Technical Assistance Publication Series

TAP 32

Clinical Drug 

Testing in 

Primary Care

 32

TAP

Technical Assistance Publication Series

Clinical Drug Testing in 

Primary Care 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Substance Abuse and Mental Health Services Administration 

Center for Substance Abuse Treatment

1 Choke Cherry Road 

Rockville, MD 20857
Clinical Drug Testing in Primary Care

ii 

Acknowledgments 

This publication was prepared for the

Substance Abuse and Mental Health 

Services Administration (SAMHSA), by

RTI International and completed by the

Knowledge Application Program (KAP),

contract numbers 270-04-7049 and 270­

09-0307, a Joint Venture of The CDM 

Group, Inc., and JBS International, Inc.,

with SAMHSA, U.S. Department of Health

and Human Services (HHS). Christina

Currier served as the Contracting Officer’s

Representative. 

Disclaimer 

The views, opinions, and content of this

publication are those of the authors and do

not necessarily reflect the views, opinions, or

policies of SAMHSA or HHS. 

Public Domain Notice 

All materials appearing in this publication

except those taken from copyrighted

sources are in the public domain and may

be reproduced or copied without permission

from SAMHSA. Citation of the source is 

appreciated. However, this publication may

not be reproduced or distributed for a fee

without the specific, written authorization

of the Office of Communications, SAMHSA, 

HHS. 

Electronic Access and Copies 

of Publication 

This publication may be ordered from

SAMHSA’s Publications Ordering Web page 

at http://store.samhsa.gov. Or, please call

SAMHSA at 1-877-SAMHSA-7 (1-877-726­

4727) (English and Español). The document

may be downloaded from the KAP Web site at

http://kap.samhsa.gov. 

Recommended Citation 

Substance Abuse and Mental Health Services 

Administration. Clinical Drug Testing 

in Primary Care. Technical Assistance 

Publication (TAP) 32. HHS Publication No.

(SMA) 12-4668. Rockville, MD: Substance

Abuse and Mental Health Services 

Administration, 2012. 

Originating Office 

Quality Improvement and Workforce

Development Branch, Division of Services

Improvement, Center for Substance Abuse

Treatment, Substance Abuse and Mental 

Health Services Administration, 1 Choke 

Cherry Road, Rockville, MD 20857. 

HHS Publication No. (SMA) 12-4668

Printed 2012 
iii 

Contents
 

Chapter 1—Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
 

Audience for the TAP....................................................... 1
 

Organization of the TAP .................................................... 1
 

Reasons To Use Clinical Drug Testing in Primary Care ........................... 2
 

Primary Care and Substance Use Disorders .................................... 2
 

Development of Drug Testing ................................................ 3
 

Workplace Drug Testing .................................................... 4
 

Drug Testing in Substance Abuse Treatment and Healthcare Settings .............. 5
 

Differences Between Federal Workplace Drug Testing and Clinical Drug Testing...... 6
 

Caution .................................................................. 6
 

Chapter 2—Terminology and Essential

Concepts in Drug Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
 

Drug Screening and Confirmatory Testing ..................................... 9
 

Testing Methods.......................................................... 10
 

Test Reliability........................................................... 10
 

Window of Detection ...................................................... 11
 

Cutoff Concentrations ..................................................... 12
 

Cross-Reactivity .......................................................... 12
 

Drug Test Panels ......................................................... 13
 

Test Matrix.............................................................. 14
 

Point-of-Care Tests ....................................................... 14
 

Adulterants ............................................................. 14
 

Specimen Validity Tests ................................................... 15
 
Clinical Drug Testing in Primary Care

Chapter 3—Preparing for Drug Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
 

Deciding Which Drugs To Screen and Test For ................................ 17
 

Choosing a Matrix ........................................................ 17
 

Specimen Availability .................................................. 20
 

Oral Fluid ............................................................ 20
 

Sweat ............................................................... 20
 

Blood ................................................................ 21
 

Hair................................................................. 21
 

Breath............................................................... 22
 

Meconium ........................................................... 23
 

Selecting the Initial Testing Site: Laboratory or Point-of-Care .................... 23
 

Collection Devices ..................................................... 23
 

Laboratory Tests ...................................................... 24
 

Advantages and Disadvantages of Testing in a Laboratory .................... 25
 

Considerations for Selecting a Laboratory .................................. 25
 

Point-of-Care Tests .................................................... 26
 

Advantages and Disadvantages of POCTs .................................. 27
 

Considerations for Selecting POCT Devices ................................ 28
 

Implementing Point-of-Care Testing ...................................... 29
 

Preparing Clinical and Office Staffs for Testing ............................. 30
 

Preparing a Specimen Collection Site......................................... 30
 

Chapter 4—Drug Testing in Primary Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
 

Uses of Drug Testing in Primary Care ........................................ 31
 

Monitoring Prescription Medication Use ................................... 32
 

Management of Chronic Pain With Opioids................................. 32
 

Evaluation of Unexplained Symptoms or Unexpected Responses to Treatment.... 32
 

Patient Safety......................................................... 33
 

iv 
Contents 

Pregnancy............................................................ 33
 

Psychiatric Care ...................................................... 34
 

Monitoring Office-Based Pharmacotherapy for Opioid Use Disorders ............ 34
 

Detection of Substance Use Disorders ..................................... 34
 

Initial Assessment of a Person With a Suspected SUD........................ 35
 

Talking With Patients About Drug Testing .................................... 38
 

Cultural Competency and Diversity ......................................... 39
 

Monitoring Patients ...................................................... 40
 

Patients With an SUD .................................................. 40
 

Monitoring Patients Receiving Opioids for Chronic Noncancer Pain............. 41
 

Ensuring Confidentiality and 42 CFR Part 2................................... 42
 

Preparing for Implementing Drug Testing..................................... 43
 

Collecting Specimens ................................................... 43
 

Conducting POCTs .................................................... 44
 

Interpreting Drug Test Results ............................................. 44
 

Result: Negative Specimen .............................................. 45
 

Result: Positive Specimen ............................................... 46
 

Result: Adulterated or Substituted Specimen ............................... 47
 

Result: Dilute Specimen ................................................ 48
 

Result: Invalid Urine Specimen .......................................... 48
 

Frequency of Testing ...................................................... 49
 

Documentation and Reimbursement ......................................... 49
 

Documentation ........................................................ 49
 

Reimbursement ....................................................... 50
 

Chapter 5—Urine Drug Testing for Specific Substances . . . . . . . . . . . . . . . . . . . . 51
 

Window of Detection ...................................................... 51
 

Specimen Collection....................................................... 52
 

v 
Clinical Drug Testing in Primary Care

Adulteration, Substitution, and Dilution ...................................... 52
 

Adulteration ......................................................... 52
 

Substitution .......................................................... 53
 

Dilute Specimens ...................................................... 53
 

Cross-Reactivity .......................................................... 54
 

Alcohol ................................................................. 54
 

Amphetamines ........................................................... 55
 

Barbiturates ............................................................. 56
 

Benzodiazepines.......................................................... 56
 

Cocaine ................................................................. 57
 

Marijuana/Cannabis ...................................................... 58
 

Opioids ................................................................. 58
 

Other Substances of Abuse ................................................. 60
 

PCP ................................................................. 60
 

Club Drugs ........................................................... 60
 

LSD ................................................................. 61
 

Inhalants ............................................................ 61
 

Appendix A—Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
 

Appendix B—Laboratory Initial Drug-Testing Methods . . . . . . . . . . . . . . . . . . . . 71
 

Appendix C—Laboratory Confirmatory Drug-Testing Methods . . . . . . . . . . . . . . 73
 

Appendix D—Laboratory Specimen Validity-Testing Methods . . . . . . . . . . . . . . 75
 

Appendix E—Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
 

Appendix F—Expert Panel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
 

Appendix G—Consultants and Field Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
 

Appendix H—Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
 

vi 
Exhibits 

Exhibit 1-1. U.S. Department of Health and Human Services

Federal Mandatory Workplace Guidelines Cutoff Concentrations

for Initial and Confirmatory Drug Tests in Urine ............................. 5
 

Exhibit 1-2. Comparison of Federal Workplace

Drug Testing and Clinical Drug Testing .................................... 7
 

Exhibit 2-1. Window of Detection for Various Matrices .......................... 12
 

Exhibit 3-1. Advantages and Disadvantages

of Different Matrices for Drug Testing ..................................... 18
 

Exhibit 3-2. Comparison of Laboratory Tests and POCTs ........................ 24
 

Exhibit 3-3. Federal and State Regulations .................................... 25
 

Exhibit 4-1. Motivational Interviewing Resources .............................. 35
 

Exhibit 4-2. The CAGE-AID Questions ....................................... 36
 

Exhibit 4-3. Brief Intervention Elements: FRAMES............................. 36
 

Exhibit 4-4. Patient Flow Through Screening

and Referral in Primary Care ........................................... 37
 

Exhibit 5-1. Barbiturates—Window of Detection ............................... 56
 

Exhibit 5-2. Benzodiazepines—Window of Detection ............................ 57
 

Exhibit 5-3. Opioids—Window of Detection .................................... 59
 

vii 

1 

Chapter 1—Introduction
 

In This Chapter 

•		 Audience for the Tap 

•		 Organization of the

Tap 

•		 Reasons To Use 

Clinical Drug Testing

in Primary Care 

•		 Primary Care and

Substance Use 

Disorders 

•		 Development of Drug

Testing 

•		 Workplace Drug

Testing 

•		 Drug Testing in

Substance Abuse 

Treatment and 

Healthcare Settings 

•		 Differences Between 

Federal Workplace

and Clinical Drug

Testing 

•		 Caution 

Audience for the TAP 

This Technical Assistance Publication (TAP), Clinical Drug 

Testing in Primary Care, is for clinical practitioners—

physicians, nurse practitioners, and physician assistants—

who provide primary care in office settings and community

health centers. The publication provides information that

practitioners need when deciding whether to introduce drug

testing in their practices and gives guidance on implementing

drug testing. 

The TAP does not address drug testing for law enforcement

or legal purposes, nor does it include testing for the use of

anabolic steroids or performance-enhancing substances.

This TAP describes some of the ways that drug testing can

contribute to the assessment, diagnosis, and treatment

of patients seen in primary care, the management of the

treatment of chronic pain, and the identification and

treatment of substance use disorders. 

Organization of the TAP 

This chapter briefly describes the role of drug testing in

primary care settings and its historical roots in workplace

testing. Chapter 2 defines the terms and practices used in

drug testing. Chapter 3 presents the mechanics of testing

and describes the steps that primary care practitioners can

take to prepare themselves, their staffs, and their office

spaces for drug testing. Chapter 4 provides information

about implementing testing in clinical practice. Important

aspects of urine drug testing for specific drugs are presented

in Chapter 5. Appendices A–H include the bibliography;

overviews of technical information on specific tests used

for initial or screening tests, confirmatory tests, and

specimen validity tests; a glossary of terms; the members

of the expert panel, consultants, and field reviewers; and

acknowledgments. 
Clinical Drug Testing in Primary Care

2 

Reasons To Use Clinical Drug 

Testing in Primary Care 

The term drug testing can be confusing

because it implies that the test will detect

the presence of all drugs. However, drug

tests target only specific drugs or drug

classes and can detect substances only

when they are present above predetermined

thresholds (cutoff levels). The term drug 

screening can also be deceptive because it

is often used to describe all types of drug

testing. However, drug screening is usually

used in forensic drug testing to refer to the

use of immunoassay tests to distinguish

specimens that test negative for a drug and/or 

metabolite from positive specimens. For the

purpose of this TAP, the term drug testing is 

used. 

When used appropriately, drug testing can

be an important clinical tool in patient care.

The types of clinical situations in which

clinical drug testing can be used include

pain management with opioid medications,

office-based opioid treatment, primary

care, psychiatry, and other situations when

healthcare providers need to determine

alcohol or other substance use in patients.

Drug testing is also used to monitor patients’

prescribed medications with addictive

potential. Patients sometimes underreport

drug use to medical professionals (Chen,

Fang, Shyu, & Lin, 2006), making some

patients’ self-reports unreliable. Drug

test results may provide more accurate

information than patient self-report.

Although drug testing can be a useful tool

for making clinical decisions, it should not be

the only tool. When combined with a patient’s

history, collateral information from a spouse

or other family member (obtained with

permission of the patient), questionnaires,

biological markers, and a practitioner’s

clinical judgment, drug testing provides

information that: 

• Can affect clinical decisions on a patient’s

substance use that affects other medical 

conditions. 

•		Can affect clinical decisions about 

pharmacotherapy, especially with

controlled substances. 

•		 Increases the safety of prescribing

medications by identifying the potential for

overdose or serious drug interactions. 

•		Helps clinicians assess patient use of

opioids for chronic pain management or

compliance with pharmacotherapy for

opioid maintenance treatment for opioid

use disorders. 

• Helps the clinician assess the efficacy of

the treatment plan and the current level

of care for chronic pain management and

substance use disorders (SUDs). 

•		Prevents dangerous medication

interactions during surgery or other

medical procedures. 

•		Aids in screening, assessing, and

diagnosing an SUD, although drug testing

is not a definitive indication of an SUD. 

• Identifies women who are pregnant, or who

want to become pregnant, and are using

drugs or alcohol. 

• Identifies at-risk neonates. 

•		Monitors abstinence in a patient with a

known SUD. 

• Verifies, contradicts, or adds to a patient’s

self-report or family member’s report of

substance use. 

• Identifies a relapse to substance use. 

Primary Care and Substance Use 

Disorders 

Practitioners can use drug testing to help

monitor patients’ use of prescribed scheduled

medications, as part of pharmacovigilance,

and to help identify patients who may need

an intervention for SUDs. 

For the purpose of this TAP, substances 

refers to alcohol and drugs that can be

abused. As defined by the Diagnostic and 

Statistical Manual of Mental Disorders, 
3 

Chapter 1―Introduction

Fourth Edition, Text Revision (DSMIV-TR; American Psychiatric Association

[APA], 2000), a substance-related disorder 

is a disorder related to the consumption of

alcohol or of a drug of abuse (APA, 2000). 

Substance use disorders (SUDs) includes

both substance dependence and substance

abuse (APA, 2000). Substance dependence

refers to “a cluster of cognitive, behavioral,

and physiological symptoms indicating that

the individual continues use of the substance 

despite significant substance-related

problems. There is a pattern of repeated selfadministration that can result in tolerance, 

withdrawal, and compulsive drug-taking

behavior” (APA, 2000). Substance abuse 

refers to “a maladaptive pattern of substance

use manifested by recurrent and significant

adverse consequences related to the repeated

use of substances” (APA, 2000). In this TAP,

the term substance abuse is sometimes used 

to denote both substance abuse and substance 

dependence as they are defined in the DSMIV-TR (APA, 2000). 

SUDs can have serious medical complications

and serious psychosocial consequences and

can be fatal. Treatment of other medical 

disorders (e.g., HIV/AIDs, pancreatitis,

hypertension, diabetes, liver disorders) may

be complicated by the presence of an SUD.

As the front line in health care, medical 

practitioners are ideally situated to identify

substance use problems. The 2009 National

Survey on Drug Use and Health (Substance

Abuse and Mental Health Services 

Administration [SAMHSA], 2010a) found that 

23.5 million (9.3 percent) persons ages 12 or

older needed treatment for an illicit drug1 

or alcohol use problem. Of this population,

only 2.6 million (1.0 percent) persons ages

12 or older (11.2 percent of those who needed

treatment) received treatment at a specialty

facility. Thus, 20.9 million (8.3 percent) of the

population age 12 or older needed substance

abuse treatment but did not receive it in the 

past year (SAMHSA, 2010a). Therefore, a

visit to a primary care practitioner may be

an excellent opportunity for such people to be 

diagnosed with SUDs. Moreover, the number

of people ages 12 or older seeking help for

SUDs from a doctor in private practice

increased from 460,000 in 2005 to 672,000 in 

2008 (SAMHSA, 2006; SAMHSA, 2009). 

Despite the potential benefits of drug testing

(such as monitoring pain medication) to

patient care, few primary care practitioners

use it. For example, a small study conducted

on the medical management of patients with

chronic pain in family practices found that

only 8 percent of physicians surveyed used

drug testing (Adams et al., 2001). 

1 Includes the nonmedical use of prescription-type 

pain relievers, tranquilizers, stimulants, and sedatives. 

Development of Drug Testing 

Drug testing performed for clinical reasons

differs substantially from workplace drug

testing programs. However, clinical drug

testing draws on the experience of Federal

Mandatory Workplace Drug Testing and,

to understand drug testing, a review of

workplace drug testing may be helpful. An

important reason for clinical practitioners

to become familiar with Federal Mandatory

Workplace Drug Testing is that the majority

of drug testing is done for workplace

purposes. For this reason, most laboratories

and many point-of-care tests (POCTs) use

the cutoff concentrations established by the

Mandatory Guidelines for Federal Workplace

Drug Testing Programs, discussed in Chapter 2. 

There are three categories of drug testing:

(1) federally regulated for selected Federal

employees (including military personnel

and those in safety-sensitive positions);

(2) federally regulated for non-Federal

employees in safety-sensitive positions (i.e.,

airline and railroad personnel, commercial

truckers, school bus drivers); and (3)

nonregulated for non-Federal employees.

Commercial truck drivers, railroad employees

and airline personnel make up the largest

group of individuals being drug tested. 

The purpose of both Federal (always

regulated) and non-Federal (may be

nonregulated) workplace drug testing is to

ensure safety in the workplace by preventing 
Clinical Drug Testing in Primary Care

4 

the hiring of individuals who use illicit drugs

and identifying employees who use illicit

drugs. 

Workplace Drug Testing 

Drug-testing methods have been available

for approximately 50 years (Reynolds, 2005).

Because of drug use in the U.S. military, by

1984, the military established standards for

laboratories and testing methods and created

the first system for processing large numbers

of drug tests under strict forensic conditions

that could be defended in a court of law. 

In 1986, an Executive Order initiated the 

Federal Drug-Free Workplace Program that

defined responsibilities for establishing a

plan to achieve drug-free workplaces. In

1987, Public Law 100-71 outlined provisions

for drug testing programs in the Federal

sector. In 1988, Federal mandatory guidelines 

set scientific and technical standards for 

testing Federal employees. In 1989, the U.S.

Department of Transportation (DOT) issued

regulations requiring the testing of nearly 7

million private-sector transportation workers

in industries regulated by DOT. 

The Federal mandatory guidelines included

procedures, regulations, and certification

requirements for laboratories; outlined the

drugs for which testing was to be performed;

set cutoff concentrations; and stated reporting

requirements that included mandatory medical

reviews by a specially trained physician

Medical Review Officer (MRO). Because a

positive result does not automatically identify

an employee or job applicant as a person

who uses illicit drugs, the MRO interviews

the donor to determine whether there is an 

alternative medical explanation for the drug

found in the specimen. The Federal mandatory

guidelines recommended that the initial

screening test identify the presence of the

following commonly abused drugs or their 

metabolites (SAMHSA, 2008): 

•		Amphetamines (amphetamine,

methamphetamine) 

•		Cocaine metabolites 

•		Marijuana metabolites 

•		Opiate metabolites (codeine, morphine) 

•		Phencyclidine (PCP) 

These substances are generally called the

“Federal 5,” but over the years they have also

been called the “NIDA 5” and “SAMHSA 5.” 

The Federal mandatory guidelines have been

updated and revised over the years to reflect

technological and process changes (Exhibit

1-1). The guidelines, last updated in 2008

(effective May 1, 2010), are available at http://

dwp.samhsa.gov/DrugTesting/Level_1_Pages/

mandatory_guidelines5_1_10.html. 

Revisions for testing of other matrixes (e.g.,

hair, oral fluid, sweat) and the use of POCTs

were proposed in 2004 (SAMHSA, 2008), but

have not been finalized. 

Although Federal agencies are required

to have drug-free workplace programs for

their employees, private-sector employers

that do not fall under Federal regulations

can establish their own drug-free workplace

programs and establish their own

regulations, testing matrices, and testing

methods. Non-Federal employees can be

tested for a broader range of drugs than the

federally mandated drugs. Many States have

laws and regulations that affect when, where,

and how employers can implement drug-free

workplace programs (search in http://www.

dol.gov). 

Laboratories are accredited by the National

Laboratory Certification Program (NLCP)

to meet the minimum requirements of the

Federal mandatory guidelines. This program

resides in SAMHSA in the Department of

Health and Human Services (HHS). 
Chapter 1―Introduction

Exhibit 1-1. U.S. Department of Health and Human Services Federal Mandatory Workplace 


Guidelines Cutoff Concentrations for Initial and Confirmatory Drug Tests in Urine
 

Initial Test Analyte Federal Cutoff 

Concentrations (ng/mL) 

Marijuana metabolites 50 

Cocaine metabolites 150 

Opiate metabolites (codeine/morphine1

) 2,000 

6-Acetylmorphine (6-AM) 10 

Amphetamines2

 (Amphetamine /methamphetamine) 500 

Phencyclidine (PCP) 25 

Methylenedioxymethamphetamine (MDMA) 500 

Confirmatory Test Analyte Federal Cutoff 

Concentrations (ng/mL) 

Amphetamine 250 

Methamphetamine3 250 

MDMA 250 

Methylenedioxyamphetamine (MDA) 250 

Methylenedioxyethylamphetamine (MDEA) 250 

Cannabinoid metabolite (delta-9-tetrahydrocannabinol-9-carboxylic acid) 15 

Cocaine metabolite (benzoylecgonine) 100 

Codeine 2,000 

Morphine 2000 

6-Acetylmorphine (6-AM) 10 

PCP 25 

Source: SAMHSA (2008).
 

1

 Morphine is the target analyte for codeine/morphine testing.
 

2

 Methamphetamine is the target analyte for amphetamine/methamphetamine testing.
 

3

 To be reported positive for methamphetamine, a specimen must also contain amphetamine at a concentration equal to, or greater 


than, 100 ng/mL. 

Drug Testing in Substance Abuse 

Treatment and Healthcare Settings 

Substance abuse treatment programs

use drug testing extensively. Drug

testing for patient monitoring in SUD

treatment programs began considerably

before workplace drug testing and has

become an integral part of many drug

treatment programs for patient evaluation

and monitoring. By 1970, the Federal

Government implemented specific mandatory

testing requirements for treatment programs

that were licensed by the U.S. Food and

Drug Administration to dispense methadone

or that received Federal funds. During the

1970s, Federal agencies developed a program

to monitor laboratories performing drug 

testing for drug treatment programs under

Federal mandates. 

Drug testing in SUD treatment is: 

•		Part of the initial assessment of a patient

being evaluated for a diagnosis of an SUD; 

•		A screen to prevent potential adverse

effects of pharmacotherapy (e.g., opioid

screen prior to starting naltrexone); 

•		A component of the treatment plan for an

SUD; 

• A way to monitor the patient’s use

of illicit substances or adherence to 

pharmacotherapy treatment for SUDs; and 

• A way to assess the efficacy of the

treatment plan (i.e., level of care). 

5 
Clinical Drug Testing in Primary Care

6 

Drug testing can also be used to document

abstinence for legal matters, disability

determinations, custody disputes, or

reinstatement in certain professions (e.g.,

lawyers, healthcare providers, airline pilots). 

Drug testing is also useful in healthcare

settings: 

•		For determining or refuting perinatal

maternal drug use; 

•		As an adjunct to psychiatric care and

counseling; 

•		For monitoring medication compliance

during pain treatment with opioids; 

•		For monitoring other medications that

could be abused or diverted; and 

•		To detect drug use or abuse where it may

have a negative impact on patient care in

other medical specialties. 

See Chapter 4 for more information about the

use of drug testing in clinical situations. 

Differences Between Federal 

Workplace Drug Testing and 

Clinical Drug Testing 

Important distinctions exist between drug

testing in Federal workplace settings and 

drug testing in clinical settings (Exhibit 1-2).

Despite the differences, Federal workplace

drug-testing guidelines and cutoff

concentrations continue to influence clinical 

drug testing. For example, many laboratories

and POCT devices test either for the federally

mandated drugs or for the same drugs, but

using modified cutoff concentrations as the

default drug-testing panel. These panels are

not suitable for clinical drug testing because

these panels do not detect some of the most

commonly prescribed pain medications, such

as synthetic opioids (e.g., hydrocodone) and

anxiolytics (e.g., benzodiazepines, such as

alprazolam), or other drugs of abuse. Initial

screening test cutoffs may not be low enough

for clinical practice in some instances (e.g.,

cannabinoids, opiates, amphetamines). 

Caution 

Trends in drug use and abuse change over

time and can necessitate a change in drug

testing panels. The technology for drug

testing evolves quickly, new drug-testing

devices become available, and old tests are 

refined. Although this TAP presents current

information, readers are encouraged to

continue to consult recent sources. Wherever 

possible, the TAP refers readers to resources

that provide up-to-date information. 
Chapter 1―Introduction

Exhibit 1-2. Comparison of Federal Workplace Drug Testing and Clinical Drug Testing 

Component Federal Workplace Testing Clinical Testing 

Specimen •	 Urine •	 Primarily urine, some oral fluid tests 

Collection 

Procedures 

•	 Federal regulations stipulate specimen 

collection procedures. 

•	 Policies minimize mistaken identity of 

specimens and specimen adulteration. 

For example, in criminal cases, 

chain-of-custody policies require 

identification of all persons handling 

specimen packages. In administrative 

cases (e.g., workplace testing), specimen 

packages may be handled without 

individual identification. Only those persons 

handling the specimen itself need to be 

identified. 

•	 Practitioners and clinical staff (hospital or clinical 

laboratory) follow procedures for properly 

identifying and tracking specimens. 

•	 In general, rigorous protocols are not used. 

Chain of custody usually is not required; 

however, laboratories under College of American 

Pathologists accreditation and/or State licensure 

should have specimen collection, handling, and 

storage protocols in place. 

Specimen 

Validity Testing 

•	 Extensive testing verifies that specimen 

substitution or adulteration has not 

occurred. 

•	 In general, laboratories do not conduct the 

same validity testing as is required for Federal 

workplace testing. 

•	 Validation often is not required with clinical use 

of POCT. 

•	 Some laboratories record the temperature of 

the specimen and test for creatinine and specific 

gravity of urine specimens. 

•	 Pain management laboratories may have 

specimen validity testing protocols that involve 

creatinine with reflexive specific gravity, pH, 

and/or oxidants in place. 

Confirmatory 

Methods 

•	 Gas chromatography/mass spectrometry 

(GC/MS) 

•	 GC/MS, liquid chromatography/mass 

spectrometry (LC/MS), liquid chromatography/ 

mass spectrometry/mass spectrometry LC/MS/ 

MS. 

Testing for 

Predetermined 

Substances 

•	 Testing is for the federally mandated drugs. •	 No set drug testing panel. 

•	 Drugs tested vary by laboratory and within 

laboratories. 

•	 Clinicians may specify which drugs are tested for 

and usually select panels (menus) that test for 

more than the federally mandated drugs. Various 

panels exist (e.g., pain). 

Cutoff 

Concentrations 

•	 Cutoff concentrations have been 

established for each drug. 

•	 A test detecting a concentration at or 

above the cutoff is considered to be a 

positive result; a test detecting nothing, 

or a concentration below the cutoff, is 

considered to be a negative result. 

•	 Cutoff concentrations vary. 

•	 In some circumstances, test results below the 

cutoff concentration may be clinically significant. 

•	 Urine and oral fluid drug concentrations are 

usually not well correlated with impairment 

or intoxication, but may be consistent with 

observed effects. 

Laboratory 

Certification 

•	 Testing must be conducted at an HHS, 

SAMHSA-certified laboratory. 

•	 Laboratories do not need HHS certification. 

However, clinical laboratories in the United 

States and its territories must be registered with 

Clinical Laboratory Improvement Amendments 

(CLIA) and comply with all State and local 

regulations concerning specimen collection, 

clinical laboratory testing, and reporting. 

•	 POCT using kits calibrated and validated 

by manufacturers does not require CLIA 

certification. 

Medical Review •	 A physician trained as an MRO must 

interpret and report results. 

•	 MRO review is not required. 

7 

9 

Chapter 2—Terminology and Essential 

Concepts in Drug Testing 

In This Chapter 

• Drug Screening and

Confirmatory Testing 

• Testing Methods 

• Test Reliability 

• Window of Detection 

• Cutoff Concentrations 

• Cross-Reactivity 

• Drug Test Panels 

• Test Matrix 

• Point-of-Care Tests 

• Adulterants 

• Specimen Validity

Tests 

Drug Screening and Confirmatory Testing 

Traditionally, drug testing usually, but not always, involves

a two-step process: an initial drug screen that identifies

potentially or presumptively positive and negative specimens,

followed by a confirmatory test of any screened positive 

assays. 

Screening tests (the initial tests) indicate the presence

or absence of a substance or its metabolite, but also can 

indicate the presence of a cross-reacting, chemically similar

substance. These are qualitative analyses—the drug (or drug

metabolite) is either present or absent. The tests generally

do not measure the quantity of the drug or alcohol or its

metabolite present in the specimen (a quantitative analysis).

Screening tests can be done in a laboratory or onsite

(point-of-care test [POCT]) and usually use an immunoassay

technique. Laboratory immunoassay screening tests are

inexpensive, are easily automated, and produce results

quickly. Screening POCT immunoassay testing devices are

available for urine and oral fluids (saliva). Most screening

tests use antigen–antibody interactions (using enzymes,

microparticles, or fluorescent compounds as markers) to

compare the specimen with a calibrated quantity of the

substance being tested for (Center for Substance Abuse

Treatment, 2006b). 

Confirmatory tests either verify or refute the result of the

screening assay. With recent improvements in confirmation

technology, some laboratories may bypass screening tests

and submit all specimens for analysis by confirmatory

tests. It is the second analytical procedure performed on

a different aliquot, or on part, of the original specimen to

identify and quantify the presence of a specific drug or drug

metabolite (Substance Abuse and Mental Health Services

Administration [SAMHSA], 2008). Confirmatory tests use

a more specific, and usually more sensitive, method than do 

screening tests and are usually performed in a laboratory.

Confirmatory tests usually: 

• Provide quantitative concentrations (e.g., ng/mL) of specific 

substances or their metabolites in the specimen. 

• Have high specificity and sensitivity. 
Clinical Drug Testing in Primary Care

10 

•		Require a trained technician to perform

the test and interpret the results. 

• Can identify specific drugs within drug

classes. 

In clinical situations, confirmation is not 

always necessary. Clinical correlation is

appropriate. For example, if the patient

or a family member affirms that drug use

occurred, a confirmation drug test is not

usually needed. 

A POCT, performed where the specimen is

collected, is a screening test. A confirmatory

drug test is usually more technically complex

and provides definitive information about

the quantitative concentrations (e.g., ng/mL)

of specific drugs or their metabolites in the

specimen tested. However, the term drug 

screening or testing is misleading in that it

implies that all drugs will be identified by

tests, whereas the drug or drug metabolites

detected by a test depend on the testing

method and the cutoff concentration. 

In Federal workplace testing, all positive

initial screening test results must be followed

by a confirmatory test (SAMHSA, 2008).

In clinical settings, however, confirmatory

testing is at the practitioner’s discretion.

Laboratories do not automatically perform

confirmatory tests. When a patient’s

screening test (either a POCT or laboratory

test) yields unexpected results (positive

when in substance use disorder (SUD)

treatment, or negative if in pain management

treatment), the practitioner decides whether

to request a confirmatory test. In addition,

a confirmatory test may not be needed;

patients may admit to drug use or not taking

scheduled medications when told of the 

drug test results, negating the necessity

of a confirmatory test. However, if the

patient disputes the unexpected findings, a

confirmatory test should be done. Chapter 4

provides information that can be helpful in

deciding whether to request a confirmatory 

test. 

Testing Methods 

Conventional scientific techniques are

used to test specimens for drugs or drug

metabolites. Most commonly, immunoassay

testing technology is used to perform the

initial screening test (Meeker, Mount, &

Ross, 2003). Appendix B, Laboratory Initial

Drug-Testing Methods, briefly describes these

methods. 

The most common technologies used to

perform the confirmatory test are gas

chromatography/mass spectrometry, liquid

chromatography/mass spectrometry, and

various forms of tandem mass spectrometry.

Information about these methods and other 

confirmatory testing methods are in Appendix 

C, Laboratory Confirmatory Drug-Testing

Methods. Other testing methods are used to

detect adulteration or substitution. Appendix

D, Laboratory Specimen Validity-Testing

Methods, provides a short explanation of

methods for specimen validity testing. 

Test Reliability 

Both POCTs and laboratory tests are

evaluated for reliability. Two measures

of test reliability are sensitivity and 

specificity, which are statistical measures 

of the performance of a test. The sensitivity

indicates the proportion of positive results

that a testing method or device correctly

identifies. For drug testing, it is the test’s

ability to reliably detect the presence of a

drug or metabolite at or above the designated

cutoff concentration (the true-positive

rate). Specificity is the test’s ability to

exclude substances other than the analyte

of interest or its ability not to detect the

analyte of interest when it is below the cutoff

concentration (the true-negative rate). It

indicates the proportion of negative results

that a testing method or device correctly

identifies. 
11 

Chapter 2—Terminology and Essential Concepts in Drug Testing

Tests are designed to detect whether a

specimen is positive or negative for the

substance. Four results are possible: 

•		True positive: The test correctly detects the 

presence of the drug or metabolites. 

•		False positive: The test incorrectly detects

the presence of the drug when none is 

present. 

• True negative: The test correctly confirms

the absence of the drug or metabolites. 

•		False negative: The test fails to detect the

presence of the drug or metabolites. 

Confirmatory tests must have high

specificity. Generally, screening tests have

relatively low specificity. Screening tests are

manufactured to be as sensitive as possible,

while minimizing the possibility of a falsepositive result (Dolan, Rouen, & Kimber,

2004). Notable exceptions from common

manufacturers of laboratory-based or pointof-care immunoassay kits are cannabinoids,

cocaine metabolite, oxycodone/oxymorphone,

methadone, and methadone metabolite 

(EDDP, or 2-ethylidine-1,5-dimethyl-3,3­

diphenylpyrrolidine). Other examples may

exist. With the exceptions noted previously,

they cannot reliably exclude substances other

than the substance of interest (the analyte),

and they cannot reliably discriminate among

drugs of the same class. For example, a lowspecificity test may reliably detect morphine,

but be unable to determine whether the drug

used was heroin, codeine, or morphine. 

Generally, the cutoff level for initial screening

tests is set to identify 95–98 percent of

true-negative results, and 100 percent of

true-positive results. Confirmatory test

cutoff concentrations are set to ensure that 

more than 95 percent of all specimens with

screened positive results are confirmed as

true positives (Reynolds, 2005). However,

confirmation rates are highly dependent upon

the analyte. For cannabinoids and cocaine

metabolite, the confirmatory rate usually

exceeds 99 percent. The clinically important

point is that false positives are rare for

cocaine metabolite or cannabinoids. 

Window of Detection 

The window of detection, also called the 

detection time, is the length of time the

substances or their metabolites can be 

detected in a biological matrix. It part, it

depends on: 

•		Chemical properties of the substances for

which the test is being performed; 

•		 Individual metabolism rates and excretion 

routes; 

•		Route of administration, frequency of use,

and amount of the substance ingested; 

• Sensitivity and specificity of the test; 

•		Selected cutoff concentration; 

• The individual’s health, diet, weight,

gender, fluid intake, and pharmacogenomic

profile; and 

•		The biological specimen tested. 

All biological matrices may show the presence

of both parent drugs and their metabolites

(Warner, 2003). Drug metabolites usually

remain in the body longer than do the parent

drugs. Blood and oral fluid are better suited

for detecting the parent drug; urine is most

likely to contain the drug’s metabolites.

Exhibit 2-1 provides a comparison of

detection periods used for various matrices. 

Many factors influence the window of

detection for a substance. Factors include, 

but are not limited to, the frequency of drug

use (chronic or acute), the amount taken, the

rate at which the substance is metabolized 

(including pharmacogenomic abnormalities,

such as mutations of CYP2D6 and other 

drug-metabolizing enzymes [White & Black,

2007]), the cutoff concentration of the test,

the patient’s physical condition and, in many

cases, the amount of body fat. 
Exhibit 2-1. Window of Detection for Various Matrices 

 

Matrix Time* 

Breath 

Blood 

Oral Fluid 

Urine 

Sweat† 

Hair‡ 

Meconium

 Minutes Hours Days Weeks Months Years 

Clinical Drug Testing in Primary Care

12 

*Very broad estimates that also depend on the substance, the amount and frequency of the substance taken, and other factors 

previously listed. 

†As long as the patch is worn, usually 7 days. 

‡7–10 days after use to the time passed to grow the length of hair, but may be limited to 6 months hair growth. However, most 

laboratories analyze the amount of hair equivalent to 3 months of growth. 

Sources: Adapted from Cone (1997); Dasgupta (2008). 

Cutoff Concentrations 

The administrative cutoff (or threshold) of a

drug test is the point of measurement at or

above which a result is considered positive

and below which a result is considered 

negative. This level is established on the

basis of the reliability and accuracy of

the test and its ability to detect a drug or

metabolite for a reasonable period after drug

use (see Test Reliability). 

Before the establishment of the Federal 

mandatory guidelines, cutoff concentrations

for screening tests were determined by the

manufacturer of the test or the laboratory.

Because the majority of drug testing is done

for workplace purposes, most laboratories

and many POCTs use the Federal mandatory

guidelines for workplace testing cutoff

concentrations. However, Federal cutoff 

concentrations are not appropriate for

clinical use. Practitioners need to know the 

cutoff concentrations used in the POCTs, 

or by the laboratory testing their patients’

specimens, and should understand which

analyte and at what cutoff the test is

designed to detect. 

Detection thresholds for Federal, employer,

and forensic drug testing panels are set high

enough to detect concentrations suggesting

drug abuse, but they do not always detect

therapeutic concentrations of medications.

For example, the threshold for opiates in

federally mandated workplace urine drug

screening is 2000 ng/mL. The usual screening

threshold for opiates in clinical monitoring

is much lower, at 300 ng/mL for morphine,

hydrocodone, and codeine (Christo et al.,

2011) to detect appropriate use of opioid pain

medication. 

For laboratory tests, practitioners can

request lower cutoff concentrations than

are commonly used in workplace testing.

However, in some cases, the error rate 

increases as the cutoff concentration 

decreases. 

Cross-Reactivity 

Cross-reactivity occurs when a test cannot 

distinguish between the substances being

tested for and substances that are chemically

similar. This is a very important concept

when interpreting test results. 
13 

Chapter 2—Terminology and Essential Concepts in Drug Testing

Drug class-specific immunoassay tests

compare the structural similarity of a

drug or its metabolites with specially

engineered antibodies. The ability to detect

the presence of a specific drug varies with

different immunoassay tests, depending

on the cross-reactivity of the drug with an

antibody. For example, a test for opioids may

be very sensitive to natural opioids, such

as morphine, but may not cross-react with

synthetic or semisynthetic opioids, such as

oxycodone. 

Substances other than the drug to be detected

may also cross-react with the antibody

and produce a false-positive result. Some

over-the-counter (OTC) decongestants (e.g.,

pseudoephedrine) register a positive drug

test result for amphetamine. Phentermine,

an anorectic agent, commonly yields a

false-positive initial amphetamines test.

Dextromethorphan can produce false-positive

results for phencyclidine (PCP) in some assays.

Cross-reactivity can be beneficial in clinical

testing. As an example, a urine test that

is specific for morphine will detect only

morphine in a patient’s urine. The morphinespecific test will miss opioids, such as

hydrocodone and hydromorphone. A urine

drug test or panel that is reactive to a wide

variety of opioids would be a better choice for

a clinician when looking for opioid use by a

patient. Conversely, the lack of sensitivity to

the common semisynthetic opioid, oxycodone,

is detrimental to patient care when a

clinician is reviewing the results of a “urine

drug screen” and sees “opiates negative”

when oxycodone abuse is suspected. Thus,

cross-reactivity can be a double-edged sword

in clinical practice. 

To avoid false-positive results caused by

cross-reactivity, practitioners should be

familiar with the potential for cross-reactivity

and ask patients about prescription and OTC

medication use. 

Drug-testing accuracy continues to improve.

For example, newer drug tests may correct

for interactions that have been formerly

associated with false-positive results. 

Practitioners can find some of this 

information in the instructions in the POCT 

packaging material, or they can talk with

laboratory personnel to know exactly what a

laboratory’s tests will and will not detect. 

Drug Test Panels 

A drug test panel is a list (or menu) of drugs

or drug classes that can be tested for in a

specimen. These can be ordered to identify

drugs of abuse or in pain management.

No single drug panel is suitable for all

clinical uses; many testing options exist

that can be adapted to clinical needs. These

panels are designed to monitor adherence

to pain treatment plans, to detect use

of nonprescribed pain medications, and

to screen for use of illicit drugs. Clinical

practitioners can order more comprehensive

drug test panels to identify drugs or classes of

drugs that go beyond the federally mandated

drugs for testing. Which drugs are included

in the testing menu vary greatly between

and within laboratories; laboratories differ 

in the drugs or metabolites included in their

comprehensive panel and have more than

one type of panel. Therefore, practitioners

should contact their laboratory to determine

the capabilities and usual practices of the

laboratory. It is just as important for a

clinical practitioner to know what a “urine

drug screen” will not detect as it is to know

what it will detect. Some laboratories have 

a comprehensive pain management panel

for people prescribed opioids for pain (Cone,

Caplan, Black, Robert, & Moser, 2008).

Panels can be customized for individual 

practices or patients, but using existing

test panels from the laboratory is generally

less expensive for patients and less timeconsuming for practitioners than ordering

tests for many individual substances.

However, these panels vary by laboratory

and are not standardized. However, it 

should be noted that laboratories may default

to the federally mandated drug tests if a

practitioner does not order a different test

panel. 
Clinical Drug Testing in Primary Care

14 

Panels are available in various configurations.

The more drugs on a panel, the more

expensive the test. Substances typically on

these panels include, but are not limited to: 

•		Amphetamine, methamphetamine. 

•		Barbiturates (amobarbital, butabarbital,

butalbital, pentobarbital, phenobarbital,

secobarbital). 

• Benzodiazepines (alprazolam,

chlordiazepoxide, clonazepam, clorazepate,

diazepam, flurazepam, lorazepam,

oxazepam, temazepam). 

•		 Illicit drugs (cocaine,

methylenedioxyamphetamine [MDA],

methylenedioxymethamphetamine [MDMA],

methylenedioxyethylamphetamine [MDEA],

marijuana). 

•		Opiates/opioids (codeine, dihydrocodeine,

fentanyl, hydrocodone, hydromorphone,

meperedine, methadone, morphine,

oxycodone, oxymorphone, propoxyphene). 

The practitioner should consult with the

laboratory when determining the preferred

test panels. 

The test menu for POCTs differs per

the manufacturer and the device. Most 

POCTs screen for drugs included in the

federally mandated test panel and other

drugs or metabolites. Different devices and

manufacturers offer various configurations of

drugs tested for in devices. 

Test Matrix 

A test matrix is the biological specimen used

for testing for the presence of drugs or drug

metabolites. Almost any biological specimen

can be tested for drugs or metabolites, but

the more common matrices include breath 

(alcohol), blood (plasma, serum), urine, sweat,

oral fluid, hair, and meconium. Depending

on its biological properties, each matrix

can provide different information about a

patient’s drug use. For example, the ratio

of parent drug to metabolite in each matrix

can be decidedly different, and each matrix 

has a different window of detection. Urine 

is the most widely used test matrix (Watson

et al., 2006). Detailed information about test

matrices is in Chapter 3. 

Point-of-Care Tests 

A POCT is conducted where the specimen is

collected, such as in the practitioner’s office.

POCTs use well-established immunoassay

technologies for drug detection (Watson et al.,

2006). 

POCTs: 

•		Reveal results quickly; 

•		Are relatively inexpensive ($5–$20,

depending on the POCT, the drugs or drug

metabolites tested for, and the number of 

tests purchased); 

•		Are relatively simple to perform; and 

•		Are usually limited to indicating only

positive or negative results (qualitative,

not quantitative). 

When reading the test results, it is important

to know that how quickly the test becomes

positive or the depth of the color do not

indicate quantitative results. 

A comparison of POCTs and laboratory tests

is in Chapter 3. 

Adulterants 

An adulterant is a substance patients can

add to a specimen to mask the presence of

a drug or drug metabolite in the specimen,

creating an incorrect result to hide their drug

use. Methods to detect adulterants exist, and 

most laboratories and some POCTs can detect 

common adulterants. No one adulterant 

(with the exception of strong acids, bases,

oxidizers, and reducing agents) can mask

the presence of all drugs. The effectiveness

of an adulterant depends on the amount of

the adulterant and the concentration of the 

drug in the specimen. A specimen validity 
15 

Chapter 2—Terminology and Essential Concepts in Drug Testing

test can detect many adulterants. Numerous

adulterants are available, especially for urine

(see Chapter 5). 

Specimen Validity Tests 

Specimen validity tests determine whether a

urine specimen has been diluted, adulterated,

or substituted to obtain a negative result.

A specimen validity test can compare urine

specimen characteristics with acceptable

density and composition ranges for human

urine, detect many adulterants (e.g.,

oxidizing compounds), or test for a specific

compound (e.g., nitrite, chromium VI) at

concentrations indicative of adulteration. 

Many laboratories perform creatinine and

pH analyses of all specimens submitted for

drug testing. An adulteration panel can be

ordered that determines the characteristics 

of the urine sample (e.g., creatinine level

with reflexive specific gravity when a low

creatinine is encountered) and checks for

the presence of common adulterants. POCT

devices are available that test for specimen

validity, as well. 

Although validity testing is not required in

clinical settings, it is sometimes advisable if

the patient denies drug use. For example, a

physician treating a patient for an SUD may

want to request validity testing if the patient

exhibits signs of relapse, but has negative

test results. Point-of-care validity tests are

available, and some POCT devices also test 

for validity at the same time they test for the

drug analyte. 

Additional information on validity follows: 

• The pH for normal urine fluctuates

throughout the day, but usually ranges

between approximately 4.5 and 9.0.

Specimens outside this range are usually

reported by the laboratory as invalid.

Specimen adulteration should be suspected

if the pH level is less than 3.0 or greater

than 11.0. 

•		Creatinine is a normal constituent in urine 

at concentrations greater than or equal to

20 mg/dL. If the creatinine is less than 20

mg/dL, the specimen is tested for specific

gravity. 

•		Specific gravity of urine is a measure of 

the concentration of particles in the urine.

Only specimens whose creatinine is less

than 20 mg/dL need to be reflexively

tested for specific gravity, although

specific gravity may be an integral part of

a POCT device’s specific validity testing

panel. Specimens with a low creatinine

and an abnormal specific gravity may be

reported as dilute, invalid, or substituted,

depending on the laboratory’s reporting

policies (SAMHSA, 2008). 

If the laboratory finds the specimen is

dilute, it will report the specimen as dilute.

However, the laboratory will also report the

positive or negative test results. Depending

on the degree of dilution, an analyte may still

be detected. 

Appendix D provides more information on

laboratory specimen validity tests. 

17 

Chapter 3—Preparing for Drug Testing
 

In This Chapter 

• Deciding Which Drugs

To Screen and Test 

For 

• Choosing a Matrix 

• Selecting the

Initial Testing

Site: Laboratory or

Point-of-Care 

• Preparing a Specimen

Collection Site 

Deciding Which Drugs To Screen and Test For 

When using drug tests to screen a patient for substance use

disorders, the practitioner should test for a broad range of

drugs. Decisions about which substances to screen for can be

based on: 

•		The patient, including history, physical examination, and

laboratory findings; 

•		The substance suspected of being used; 

•		The substances used locally (the Substance Abuse and

Mental Health Services Administration’s [SAMHSA’s]

Drug Abuse Warning Network compiles prevalence data

on drug-related emergency department visits and deaths;

information is available at http://www.samhsa.gov/data/

DAWN.aspx); 

• The substances commonly abused in the practitioners’

patient population; and 

•		Substances that may present high risk for additive or

synergistic interactions with prescribed medication (e.g.,

benzodiazepines, alcohol). 

Choosing a Matrix 

Practitioners can choose among several matrices for drug

and alcohol testing for adults: urine, oral fluid, sweat, blood,

hair, and breath (alcohol only). Neonates can be tested using

meconium. Urine is the most commonly used matrix for drug

testing and has been the most rigorously evaluated (Watson

et al., 2006); it is discussed at length in Chapter 5. Exhibit

3-1 provides a brief comparison of the advantages and

disadvantages of the seven matrices. 
Clinical Drug Testing in Primary Care

Exhibit 3-1. Advantages and Disadvantages of Different Matrices for Drug Testing 

Matrix Advantages Disadvantages 

Urine •	Available in sufficient quantities 

•	Higher concentrations of parent drugs 

and/or metabolites than in blood 

•	Availability of point-of-care tests (POCTs) 

•	Well-researched testing techniques 

•	 Short to intermediate window of detection 

•	Easy to adulterate or substitute 

•	May require observed collection 

•	 Some individuals experience “shy bladder” 

syndrome and cannot produce a specimen 

Oral Fluid •	Noninvasive specimen collection 

•	Easy to collect 

•	Reduced risk of adulteration 

•	Directly observed specimen collection 

•	Parent drug rather than metabolite can be 

the target of the assay 

•	Able to detect same-day use, in some 

cases 

•	Availability of POCTs 

•	Detect residual drug in the mouth 

•	 Limited specimen volume 

•	Possibility of contamination from residual 

drug in mouth that cannot be correlated 

with blood concentrations 

•	 Short window of detection 

•	Requires supervision of patient for 10−30 

minutes before sampling 

•	 Salivation reduced by stimulant use 

•	Need for elution solvent to efficiently 

remove drugs adsorbed to collection 

device 

•	Cannabinoids in oral fluid have been shown 

to arise from contamination of the oral 

cavity rather than excretion in saliva from 

blood 

Sweat •	Detects recent use (fewer than 24 hours 

with a sweat swipe) or allows for cumulative 

testing with the sweat patch (worn for up to 

7–14 days) 

•	Noninvasive specimen collection 

•	Difficult to adulterate 

•	Requires little training to collect specimen 

•	May be an economical alternative to urine 

•	 Few facilities and limited expertise for 

testing 

•	Risk of accidental or deliberate removal of 

the sweat patch collection device 

•	Unknown effects of variable sweat excretion 

among individuals 

•	 Only a single sweat collection patch 

available so multiple analyses cannot be 

done if needed (i.e., more than one positive 

initial test) 

•	May be affected by external contaminants 

•	Requires two visits, one for patch 

placement and one for patch removal 

Blood •	Generally detects recent use 

•	Established laboratory test method 

•	Expensive, except to detect ethanol 

•	 Limited window of detection 

•	 Invasive specimen collection (venipuncture) 

•	Risk of infection 

•	Requires training to collect specimen 

•	May not be an option for individual with 

poor venous access 

18 
Chapter 3―Preparing for Drug Testing

Exhibit 3-1. Advantages and Disadvantages of Different Matrices for Drug Testing, continued 

Matrix Advantages Disadvantages 

Hair •	 Longest window of detection 

•	May be able to detect changes in drug use 

over time (from 7–10 days after drug use 

to 3 months, depending on length of hair 

tested) 

•	Directly observed specimen collection 

•	Noninvasive specimen collection 

•	 Four tests will cover 1 year 

•	Easy storage and transport 

•	Difficult to adulterate or substitute 

•	Readily available sample, depending on 

length of hair tested 

•	Cannot detect use within the previous 

7–10 days 

•	Difficult to interpret results 

•	Costly and time consuming to prepare 

specimen for testing 

•	 Few laboratories available to perform 

testing 

•	No POCTs currently available 

•	Difficult to detect low-level use (e.g., 

single-use episode) 

•	May be biased with hair color (dark 

hair contains more of some basic drugs 

[cocaine, methamphetamine, opioids] due 

to enhanced binding to melanin in hair) 

•	Possibility of environmental contamination 

•	 Specimen can be removed by shaving 

Breath •	Well-established method for alcohol testing 

•	Readily available 

•	Used only for alcohol and other volatiles 

•	 Short window of detection 

•	May be difficult to obtain adequate sample, 

especially with patients who are very 

intoxicated or uncooperative 

•	Uncommon in clinical setting 

Meconium •	Can detect maternal drug abuse and fetal 

or infant exposure 

•	Wide window of drug detection (third 

trimester of gestation) 

•	Noninvasive collection from diaper 

•	Generally, adequate specimen amount 

•	Narrow collection window that can be 

missed, especially in babies with low birth 

weight 

•	Testing not available in all laboratories 

•	Requires extra steps (weighing and 

extraction) 

•	Confirmation assays more difficult than for 

urine 

Sources: Center for Substance Abuse Treatment (2006a); Dolan, Rouen, & Kimber (2004); Kwong & Ryan (1997); Warner (2003). 

Once ingested, drugs of abuse are rapidly

distributed via the blood to all parts of the

body. Abused drugs are generally lipid

soluble and are mainly metabolized by the

liver to more water-soluble metabolites. 

These metabolites are removed from blood by

the kidneys and excreted in urine. Because

many drugs are cleared from the blood

rapidly, testing of blood or its components

(serum) has short periods of detection,

as does breath for testing for alcohol

consumption and oral fluids because the

drug passes quickly into, and is eliminated

from, breath and oral fluids. Depending on

the drug itself and previously listed factors

that affect metabolism, urine usually has a 

window of detection that is slightly longer

than oral fluid. Urine detection times vary

from less than 1 day after ingestion to several

weeks. Hair has a longer window of detection,

but is best suited for detection of heavy drug

use. The cells that generate hair absorb the

metabolites that are circulating in the blood

at the time the hair is produced; therefore,

hair has the longest window of detection,

depending on the length of the hair. It is

notable that drugs may be incorporated

into hair from external sources, such as 

mechanical contact between the hair and 

the drug. In utero drug exposure also can be

monitored with maternal and neonatal urine 

and/or hair testing. 19 
Clinical Drug Testing in Primary Care

20 

Specimen Availability 

Some specimens are more easily collected

than others. Collection of blood samples

requires trained personnel to perform

venipuncture and is more invasive than

collection of urine, oral fluid, or hair 

specimens. Collections of oral fluid and hair

are less intrusive than urine collection. 

Oral Fluid 

During the past decade, the use of oral fluid

for drug testing has been validated by a

large body of scientific literature (Bosker &

Huestis, 2009; Cone & Huestis, 2007). The

parent drug is usually found in oral fluids,

although the metabolite(s) may be present

and quite useful. The parent drug is generally

found in higher concentrations in oral fluids

than are drug metabolites. Compared with

urine specimens, oral fluid specimens present

fewer opportunities for adulteration or

substitution (Dams, Choo, Lambert, Jones, &

Huestis, 2007). Use of commercial adulterants

or mouthwashes were not found to interfere 

with the immunoassay (Bosker & Huestis,

2009), or they did not affect test results if

the products are used more than 30 minutes

before specimen collection (Drummer, 2006;

Niedbala, Kardos, & Fries, et al., 2001; 

Niedbala, Kardos, Fritch, Cannon & Davis, 

2001). The window of detection for oral

fluid is narrower than it is for urine, and 

drug concentrations are generally lower

(Warner, 2003). In general, drug testing

of oral fluids detects drug use during the

previous 24–48 hours, regardless of the route

of administration (Cone, 2006), although the

selection of cutoffs plays an important role in

the length of the detection window. 

Oral fluid collection devices vary, but the

most common version is a swab or absorbent 

pad on a stick that is placed between the

lower cheek and gums to collect fluid and

is left in place for a few minutes. It is then

inserted into a vial containing a buffer

solution for shipment to the laboratory.

POCTs are also available for oral fluid 

testing. 

On occasion, dry mouth syndrome can slow

oral fluid collection, often requiring several

minutes to collect an adequate sample

(Drummer, 2006). Some medications and

illegal drugs cause a dry mouth, and some

oral fluid collection devices assist collection 

by stimulating oral fluid flow. Patients

should not eat immediately before testing

because some food tends to inhibit oral 

fluid production. If blood is present in the

patient’s oral fluid, collection of an alternative 

specimen, such as blood or urine, would be 

needed. Oral fluid limits the number of repeat 

or confirmatory tests on the specimen because 

of the small amount of the sample, compared

with a urine sample. 

Sweat 

Several collection devices have been 

manufactured for collecting sweat specimens.

The two most common are the patch and

the swipe; however, the sweat patch is the

only device approved by the U.S. Food and

Drug Administration (FDA). The quantity of

sweat collected is determined by the length

of time the patch is worn and the physiology

of the person wearing the patch. The patch

should be worn for at least 3 days, but no

longer than 7 days, although most drugs

will have been excreted within the first 48 

hours (Barnes et al., 2009; Huestis et al.,

2008; Kacinko et al., 2005; Schwilke et al., 

2006). This ensures that a sufficient amount

of sweat is collected for testing. The sweat

collected with the patch detects drug use that

occurred shortly before the patch was applied

and while the device remains on the skin. 

The skin should be thoroughly cleaned with

soap and water and then swabbed well with

alcohol. The patch should then be applied to

the skin by a staff member, not the patient

(Watson et al., 2006). After 7 days, the patch

is removed by the practitioner and sent to the

laboratory for analysis. 

Mainly the parent drug is found in sweat;

however, some drug metabolites also may

be detected (Dasgupta, 2008). Drugs and

drug metabolites that have been detected 
21 

Chapter 3―Preparing for Drug Testing

in sweat include tetrahydrocannabinol

(THC), amphetamine, methamphetamine,

methylenedioxymethamphetamine (MDMA,

or “Ecstasy”), codeine, morphine, heroin

metabolite, phencyclidine (PCP), and cocaine

and its metabolites (e.g., benzoylecgonine,

ecgonine methyl ester) (Barnes et al., 2009;

Dasgupta, 2008). 

Because sweat can be collected only in

limited quantities, there may not be sufficient

specimen for repeat or confirmatory testing.

Sweat is less susceptible to tampering or

adulteration than is urine. The accuracy

of sweat testing is not standardized. Its

accuracy remains somewhat controversial

(Chawarski, Fiellin, O’Connor, Bernard, &

Schottenfeld, 2007; Watson et al., 2006) and

more research is needed (Barnes et al., 2009;

Huestis et al., 2008; Kacinko et al., 2005; 

Schwilke et al., 2006). However, the sweat

patch is used extensively in the criminal

justice system, and its use to identify relapse

or violations of conditions of probation has

been upheld by the courts. 

Blood 

Blood testing detects alcohol or drug use

starting shortly after use, depending on the

substance and the route of administration. In 

general, blood has a shorter detection period

than urine (Warner, 2003). Blood collection

is more invasive than other procedures and

requires trained personnel to collect the

specimen and perform laboratory testing. For

people who inject drugs, or those with poor

venous access, drawing blood may be difficult. 

Hair 

In theory, the presence of drugs in hair

is based on a simple principle: Drugs or

their metabolites circulate in a person’s

bloodstream, and the hair follicles absorb the 

drug and/or metabolites from the bloodstream

and from secretions of the sebaceous and 

sweat glands in the scalp (Cone, 1996; 

Musshoff & Madea, 2006). Trace amounts

of drug become entrapped in the core of the

hair as it grows, at a rate of approximately

1 cm per month (Dolan et al., 2004). Drug

metabolites can be detected in the hair 

shaft approximately 7–10 days after drug

ingestion. Hair is unique in that it may

provide retrospective information on drug

use, versus the point-of-time information

provided by urine, blood, and breath. (Kintz,

Villain, & Ludes, 2004). In some cases,

drugs were found to move down the hair

shaft via sweat (Henderson, Harkey, Zhou,

Jones, & Jacob, 1996), which would disrupt

the use of hair testing’s ability to determine

the historical use. Another unfortunate 

aspect of interpreting hair test results of

drugs and their metabolites is that drugs

may be incorporated into hair by simple

environmental drug exposure (Ropero-Miller 

& Stout, 2008; Wang & Cone, 1995). 

The hair sample is usually taken from the

back of the head, cut with scissors as close to 

the skin as possible (Wong & Tse, 2005). Hair

can be collected from other parts of the body

(e.g., face, armpit) of patients who are bald or

have shaved heads. 

Hair testing appears to be most reliable for

detecting prior frequent, heavy use of cocaine,

opioids, amphetamine, PCP, and Ecstasy,

but is not suited for detection of very recent

use, or occasional drug use. Musshoff and

Madea (2006) report that hair tests can

detect the presence of the THC metabolite,

tetrahydrocannabinol carboxylic acid. Hair

analysis can often distinguish between

heroin and morphine use—a distinction that

is sometimes difficult to make with blood or 

urine analysis (Dolan et al., 2004) because

of the short half-life of heroin metabolite in 

these matrices. Hair testing for alcohol is

inappropriate; alcohol does not incorporate

into hair. However, the minor metabolites of 

ethanol, ethyl glucuronide, and ethyl sulfate

in hair show promise as markers of alcohol

use (Wurst, Skipper, & Weinmann, 2003). 
Clinical Drug Testing in Primary Care

22 

Hair testing is suited to: 

•		Detecting chronic drug use (Dolan et al.,

2004; Warner, 2003); 

• Providing a view of the patient’s long-term

substance use pattern; and 

•		 Indicating periods of abstinence (Pragst &

Balikova, 2006). 

An advantage of drug testing with hair is

the longer window of detection compared

with other matrices (Boumba, Ziavrou, &

Vougiouklakis, 2006). The detection period

for hair is limited only by the length of the

hair sample and the degree of deposition in

the hair. Cannabinoids have been shown to 

deposit less readily than basic drugs in hair

(Huestis et al., 2007). Some laboratories

typically restrict analysis to a hair segment

representing about 3 months of growth.

However, this long window period is also a

disadvantage; hair testing is not useful in

substance abuse treatment or monitoring

opioid pain or other addictive medications

when frequent (weekly or monthly) drug

testing is desired. Because the timing of the

drug use is difficult to determine by testing

hair, it is not very useful clinically. 

Disadvantages for testing for drugs in hair

are the high costs and the longer time needed

to obtain results, compared with the time

required by other matrices. Analysis of the

hair specimen is a complex process that

involves breaking down the hair to free the

drugs trapped in it. This chemical process

requires a longer time of analyses than other

matrixes. It can be done only in a laboratory;

no POCTs are available for testing hair

samples. 

Some questions remain about environmental

contamination; a person may claim that

the drug is present in the hair because the

individual was in a room where others were 

smoking drugs. Therefore, in preparation

for analysis at the laboratory, the hair

sample is washed, which may remove

the contamination. Unfortunately, this 

environmental contamination cannot always

be differentiated from actual drug use, even if

drug metabolites are measured quantitatively

in hair (Ropero-Miller & Stout, 2008). 

Additional controversies exist about whether 

biophysical attributes affect hair analysis.

Studies have shown that concentrations of 

drugs in hair can be affected by variations in

hair structure, growth rate, melanin content,

hygiene, and cosmetic hair treatments, such

as bleaching (Dasgupta, 2008). Although

there have been a limited number of human 

clinical controlled studies, data show that 

higher concentrations of some drugs (e.g.,

codeine, cocaine, amphetamine) are found

in dark hair compared with concentrations

found in blond or red hair (SAMHSA, 2004).

Cone and Joseph (1996) reviewed several

articles and found that hair testing may

be biased toward some hair types. Drugs

of abuse bind more readily to Africoid and

Mongoloid types of hair compared with

Caucasoid hair. Cosmetic hair treatments 

also affect the binding of drugs to hair. For

example, bleaching of the hair can reduce

drug content, but it also can damage the hair

to the extent that bleaching may increase

binding of the drug to the hair (Skopp,

Pötsch, & Moeller, 1997). Some drugs (i.e.,

THC) do not differentially distribute into

hair based on melanin content (Smeal,

2007). Therefore, hair testing may not be

the most equitable drug testing matrix. Hair

rinses, bleaches, and shampoos that claim to

interfere with drug tests are advertised on

the Internet and in magazines. 

Breath 

Several simple-to-use, but accurate, breathtesting devices are available for detecting

very recent alcohol use. Breath also may

be employed for the identification and

quantitation of a variety of other volatiles,

especially in industrial hygiene situations.

However, breath testing is commonly used

in alcohol treatment programs, but not in

primary care. 
23 

Chapter 3―Preparing for Drug Testing

 

The body metabolizes alcohol rapidly, but

alcohol will be detectable in breath as long

as it is present in blood. The detection period

for ethyl alcohol itself is hours (not days)

after the last alcohol use. The metabolism of 

alcohol varies considerably by the person’s

gender, age, physical condition (especially the

condition of the liver), and weight. 

Easily administered breath alcohol tests

are available to confirm alcohol ingestion

within the past several hours. When a breath

alcohol analyzer test is conducted properly,

it gives an accurate measurement of breath

alcohol content (BrAC). The BrAC gives an

estimate of blood alcohol level (BAL) (Watson

et al., 2006). Body temperature and breathing

patterns can affect breath alcohol test results. 

Compared with blood and urine tests, breath

tests are less precise. Some evidence suggests

that breath tests may underestimate BALs by

approximately 8.5 percent (Garriott, 2008). 

The breath alcohol analyzer (such as the

best-known version, Breathalyzer) is a device

that gives an accurate BrAC. The benefits of

breath alcohol analyzers are that they: 

•		Are simple to use; 

•		Are inexpensive; 

•		Give instant results; and 

•		Are noninvasive. 

The National Highway Traffic Safety

Administration provides a list of breath

alcohol analyzer devices that have been

tested for accuracy and reliability. The list is

available through http://www.dot.gov/odapc. 

Meconium 

Meconium is the first few bowel movements 

of a neonate. Research shows that meconium 

provides a record of neonate exposure and

maternal substance use in the third trimester 

of gestation (Concheiro et al., 2010; Gray

& Huestis, 2007; Kacinko, Jones, Johnson, 

Choo, & Huestis, 2008). Meconium offers a

wide window of drug detection, monitoring

drug use primarily over the third trimester 

of gestation. Because collection of meconium

is noninvasive (requiring only the transfer

of the specimen or meconium from diaper to

specimen container), it is usually easier to

collect than urine. Collection of a specimen

must be made before the neonate passes the

first formed stool; for full-term babies, this 

generally occurs within 3 days (Gareri, Klein,

& Koren, 2006). 

However, this is a highly subspecialized

area that may be used in connection with

a maternal urine drug test. The testing of

meconium should be recognized as having

potential medicolegal ramifications (i.e., a

positive test may result in the State removing

the newborn from the new mother’s custody). 

Potential disadvantages to using meconium

exist. Test results vary greatly by substances

used and cutoff concentrations because of 

the unique qualities of meconium. Moreover,

laboratory methods of preparing the specimen

can affect the test results greatly (Gray &

Huestis, 2007). Urine contamination may

skew results (Gray et al., 2010). 

Selecting the Initial Testing Site: 

Laboratory or Point-of-Care 

Many factors should be considered when

deciding to test onsite with a POCT for the

initial test or offsite by a laboratory. Exhibit

3-2 compares POCTs and laboratory tests.

The sections below explain each method. 

Collection Devices 

The collection device must be single use. It

will normally be individually packaged with

collection aids and a tamper-evident security

seal. The collection device must not alter or 

affect the specimen. The device should have

the following features for each specimen

matrix: 

•		Blood. Sterile tubes that usually contain

sodium fluoride to inhibit breakdown of 

drugs. The use of “gel” or “serum separator 
tubes” for specimen collection for any type

of drug analysis is highly discouraged. 

• Hair. Foil or a plastic bag to store the

sample with an indication of proximal and

distal ends. 

• Oral fluid. Device that allows accurate 

determination of the volume collected 

(usually 1.0±0.1 mL) and that contains

an elution solvent to efficiently elute the

adsorbed drugs. 

• Sweat. A patch, placed on the skin,

typically composed of an adhesive layer,

release liner, and sweat-collection pad. 

• Urine. A plastic collection container

typically with a temperature strip outside

the container to determine specimen 

temperature. 

Shipping materials, documentation, and

order forms will be needed if the specimen is

to be sent to a laboratory. 

Exhibit 3-2. Comparison of Laboratory Tests and POCTs 

Criterion Laboratory Test POCT 

Time to Results Initial test can be available within hours, 

but the confirmatory test takes days 

Minutes 

Ease of Use Requires complex equipment Relatively simple to use 

Training Requires trained technicians or 

technologists 

Minimal training required 

Breadth of Tests Wide range of test menus Limited test menu 

Interpretation Objective quantitative results; variations 

in laboratory cutoff concentrations may 

influence interpretation 

Subjective results; requires interpretation, 

not quantitative 

Sources: Melanson (2005); Watson et al. (2006). 

Clinical Drug Testing in Primary Care

24 

Laboratory Tests 

Laboratories perform screening,

confirmatory, and validity tests, using

instrumented devices that are operated by

trained technical personnel. Laboratory

testing is more accurate than POCT and

provides quantitative information on what

drugs and/or metabolites were detected.

Laboratories use high-volume immunoassay

tests to separate negative specimens from 

those that require confirmation testing.

Confirmation tests use either liquid

chromatography (LC) or gas chromatography

(GC) in combination with mass spectrometry

(MS) for detection and measurement of drugs

and metabolites. Tandem mass spectrometry

(MS/MS) is a more sensitive form of MS.

These tests provide a laboratory with the

ability to identify and measure drugs and/

or metabolites in biological fluids at low

concentrations. Technical details about these 

tests and their strengths and limitations are

in Appendixes B–D. 

Most laboratories usually perform initial

drug tests for commonly abused drugs,

including 6-acetylmorphine (heroin

metabolite), opioids, cocaine, amphetamines,

barbiturates, PCP, and THC. Some 

laboratories offer extended opioid panels;

these laboratory tests can detect and confirm

several opioids including morphine, codeine,

hydrocodone, hydromorphone, oxycodone,

and oxymorphone. Some laboratories offer,

upon request, panels that will differentiate

individual benzodiazepines and their

metabolites. Other extended panels include

buprenorphine, carisoprodol, methadone,

fentanyl, meperidine, and propoxyphene,

among others. Not all laboratories

are capable of identifying all known

benzodiazepines and, where necessary

or appropriate, their metabolites. The

requirement for additional testing depends

in large part on the patient population 
25 

Chapter 3―Preparing for Drug Testing

served by the facilities using the laboratory

(e.g., a methadone clinic or a detoxification

facility might require methadone, EDDP

[methadone metabolite], burprenorphine/

norbuprenorphine, and/or other drug or

metabolite analyses). POCTs or laboratorybased tests may be used for the initial

testing, but only laboratories can perform

confirmatory testing. 

Advantages and Disadvantages of Testing 

in a Laboratory 

Advantages. Laboratory tests have

several important advantages over POCTs.

Laboratory tests: 

•		Generally have a higher degree of precision. 

•		May offer quantitation of drugs and/or

metabolites and a reasonable estimate of 

the timeframe in which the drug was used. 

• Can provide information on specific drugs

used. 

• Can be directly sent for confirmatory

GC/MS on the same sample. 

•		Are performed by trained laboratory

professionals. 

Disadvantages. The disadvantage of

laboratory-based tests is turnaround time.

The time required for laboratory-based

testing may include transportation of the

specimen to the laboratory, specimen aliquot

preparation, and instrument analysis time—

steps that are not required for POCTs.

Results from POCT can be available while the 

patient is still in the office, so the practitioner

can immediately discuss them with the

patient. Depending on the laboratory, clinical

screening results may be available in less

than 1 hour after receipt or the next day,

unless further testing, such as confirmation

or reflexive testing, is required. 

Considerations for Selecting a Laboratory 

Before selecting a laboratory, practitioners

should contact the laboratory and speak

directly to the director or toxicologist to

(White & Black, 2007): 

• Determine the laboratory’s analytic

capabilities (laboratories may use the

Federal Five as the testing menu for drug

screens, which may or may not include the

clinical drugs of interest); 

•		 Inquire about other panels that test for

drugs and drug classes of clinical interest; 

• Confirm that the laboratory follows

established Federal and State regulations

(Exhibit 3-3); 

• Determine whether the laboratory’s testing

procedures are appropriate for clinical use;

and 

•		Ensure that the laboratory provides

technical assistance so the practitioner can

obtain help with interpreting test results

or determining which panel to order. 

Exhibit 3-3. Federal and State Regulations 

•	The Clinical Laboratory Improvement 

Amendments (CLIA) of 1967 and of 1988 set 

forth conditions that all laboratories must meet 

to be certified to perform testing on biological 

specimens (http://www.cms.gov). 

•	The U.S. Department of Health and Human 

Services (HHS) Mandatory Guidelines for 

Federal Workplace Drug Testing Programs 

specify the requirements for a laboratory to 

be certified by the HHS National Laboratory 

Certification Program. Information is available 

at http://workplace.samhsa.gov/Dtesting.html 

•	Private and professional organizations (e.g., 

College of American Pathologists) have 

established voluntary laboratory accreditation 

programs. The American Association of 

Bioanalysts has private personnel standards. 

•	 State clinical laboratory programs operate 

under individual State laws; State programs 

are usually authorized through the Centers for 

Medicare & Medicaid Services. 
Clinical Drug Testing in Primary Care

26 

Practitioners need to talk to laboratory

personnel about: 

• Appropriate in-office specimen collection,

handling, and storage procedures for each

matrix used; 

•		Each test ordered, at least until the 

practitioner is thoroughly familiar with the

tests and drug panels the laboratory offers

(practitioners need to be sure they know

exactly what they are ordering and the

limitations of any particular test); 

•		Test results (practitioners should contact

the laboratory about unexpected results,

whether positive or negative); and 

•		Referral testing for drugs not offered by

the primary testing clinical laboratory. 

Point-of-Care Tests 

Several different types of POCTs are

available. Generally, POCTs: 

•		Use well-established immunoassay

technologies for drug detection; 

•		Determine the presence of parent drugs or

their metabolites; 

•		Sometimes can determine the validity

of a specimen, which is to be highly

recommended as an integral part of the

testing process; 

•		 Identify drug classes (e.g., opioids,

benzodiazepines, barbiturates),

single drugs, or metabolites (e.g.,

benzoylecgonine, a cocaine metabolite); and 

•		Require a few drops of a specimen. 

FDA has approved POCT devices for urine,

breath, and oral fluid testing, but devices

for urine drug testing are most widely used.

Advances are being made in developing

POCTs for other matrices, and these may be

available in the future. 

Various POCTs are available: 

•		Breath-testing devices, which are rare in

primary care practice (the patient blows

into the device) 

•		Cards or cassettes (drops of urine are

placed on a card or in wells on a cassette) 

•		Dipsticks (an absorbent strip is dipped into

the specimen) 

•		Combination collection/test cups (the

testing strip is integrated into the

collection cup, and results can be read on

the outside of the cup) 

A few devices double as both collection 

and testing devices. After the specimen

is collected, the tester initiates the test, 

carefully times the test, and interprets and

records the results. The test component of

noninstrumented POCTs is an absorbent 

strip with an antibody-dye complex. The test

is done by inserting the absorbent strip, card,

or cassette into the specimen or adding the

specimen to the testing device. When the

strip or cassette comes into contact with the

specimen, it reacts to the drug or drug class

that the POCT can detect. Generally, a line or

dot appears in the zone labeled for a specific

drug if the drug is not present (negative

test result); no line or dot appears when a

specific drug is present (positive test result).

A photocopy of the portion of the POCT device 

that is read can be made and placed in the

patient’s chart. Enough fluid (urine or oral

fluid) should be retained for any reflexive or

confirmatory testing that may be required. 

It is critical that practitioners read package

inserts carefully to know how to perform

the test and read the results. Positive POCT 

results should usually be followed by a

laboratory confirmatory test if the patient

denies drug use when confronted with the

positive results. A confirmatory test must be

done if legal or employment ramifications for

the patient will result. 
27 

Chapter 3―Preparing for Drug Testing

Advantages and Disadvantages of POCTs 

The principal advantage of POCTs is that

the results are available in approximately

10 minutes. This fast turnaround allows 

practitioners to discuss the results with the

patient during that office visit and make

clinical decisions and act appropriately that

day. This early intervention may prevent

other health problems, hospitalization, or

treatment episodes. It is also in keeping

with behavioral principles: the immediacy

of the intervention in relation to a behavior 

makes reinforcement more useful. Several 

manufacturers have developed drug-of-abuse

assays for POCT that offer similar, but

not exact, sensitivity and specificity to the

methodologies used by central laboratories

(Melanson, 2009). A variety of testing

panels with different cutoff concentrations

is available for these testing devices, but

they are not as varied as laboratory testing.

Increasingly, vendors are offering pointof-care devices that test for a wider range

of drugs and with more sensitivity and

specificity. POCTs are available to test

for amphetamine, methamphetamine,

barbiturates, benzodiazepines, cocaine,

methadone, opioids, PCP, propoxyphene,

Ecstasy, oxycodone, tricyclic antidepressants,

buprenorphine, and THC acid metabolite

(Melanson, 2005). 

A survey of five POCT immunoassay

devices for urine testing found that each

had a false-negative rate for opioids of less

that 1 percent and a false-positive rate

less than 0.25 percent for testing for pain

management (Crouch, Hersch, Cook, Frank,

& Walsh, 2002). Melanson’s (2009) review

of the literature reviewed studies looking

at the analytical performance (sensitivity,

specificity, precision, and accuracy) of

POCTs for drugs of abuse. Generally, most

studies suggested that POCTs are a reliable

method to screen for drugs of abuse and

that the results are comparable to those

from automated immunoassays and GC/MS.

However, Melanson (2009) also noted that 

some studies found inconsistencies, such as: 

•		Several devices were found to have 

discrepancies between the claims of the

manufacturer and the devices’ product

performance. 

•		Some devices deviated from their stated 

cutoffs showing positive results below the

cutoff or negative results above the cutoffs. 

However, no POCT device yields perfect

agreement with more sophisticated testing,

such as GC/MS or high-performance liquid

chromatography (Watson et al., 2006).

Disagreement between methods was highest

for samples near the cutoffs. 

Cross-reactivity differs among POCT devices

because of differing antibody specificity. The

manufacturer provides a list of compounds

tested and their degree of cross-reactivity,

including those medications outside the drug

class, which may cause false-positive results

(Melanson, 2009). 

George and Braithwaite (2002) caution

that the apparent benefit of POCTs—rapid

assessment of a patient’s drug use—can be

detrimental if treatment decisions are based 

on these rapid, but unconfirmed, results. A

disadvantage of noninstrumented POCTs

is that most test only for drug classes, not

for specific drugs within a class (Gourlay,

Caplan, & Heit, 2010), which is what is

needed more often in clinical applications.

Many POCTs have a limited test menu,

compared with laboratory testing and

in clinical settings; practitioners may

need a more complete panel, or separate

tests, to assess for specific drugs. POCT

devices do not provide quantitative drug

or metabolite information. POCT devices 

provide presumptive results only; a sample

needs to be sent for confirmatory testing at a

laboratory. Cutoffs employed by some POCT

devices may not provide adequate sensitivity.

Result interpretation may also be subjective,

making performance operator-dependent 

(Melanson, 2009). 
Clinical Drug Testing in Primary Care

28 

Considerations for Selecting POCT Devices 

Matrices. POCT devices should be FDA 

approved and usually CLIA-waived to test

urine, breath (for alcohol), and oral fluid for

substances of abuse. None are available yet

for hair, sweat, or blood for drugs of abuse,

although some POCT devices do exist for

therapeutic drugs in blood or blood products.

POCTs for urine remain the most commonly

used, despite advances in testing of other

matrices. Cutoff levels, cross-reactivity,

and other possible interferences have been

studied more for POCT urinalysis than for

any other matrix (Watson et al., 2006). Most

POCT devices are used in an environment 

that is external to a clinical laboratory. 

Regulatory Issues. The use of POCTs is 

covered by two Federal regulations. The

Medical Devices Act requires that all in vitro

medical diagnostic devices be evaluated

and cleared for use by FDA for commercial

distribution before use with patients. CLIA

regulates the use of POCTs and requires

that medical diagnostic tests and devices be

used only in laboratories that meet CLIA

standards and are certified to perform those

specific tests. However, tests may be waived

from CLIA regulatory oversight if they meet

certain requirements, primarily if they are

simple to use and interpret and have a low

error risk. 

Practitioners should be aware of the following

specific requirements when considering using

a POCT device: 

•		FDA approval. FDA has cleared several 

point-of-care devices for testing drugs of

abuse. The FDA Center for Devices and 

Radiological Health provides information

on test categorization and approval or

clearance of testing devices (http://www.

fda.gov/MedicalDevices/default.htm). 

•		Waived tests . A testing device may have

been cleared by FDA for commercial

distribution, but may not have been CLIA 

waived. FDA maintains a list of currently

waived tests (http://www.accessdata.fda.

gov/scripts/cdrh/cfdocs/cfCLIA/testswaived.

cfm). POCT manufacturers will also state

whether a test is waived by CLIA. 

•		Certificate of waiver. All sites 

performing waived tests must have a

CLIA-waiver certificate and adhere to the 

manufacturer’s instructions for performing

the test. Facilities or physicians’ offices

performing waived tests must enroll in

CLIA, pay the applicable fee, and follow

the manufacturer’s instructions. An 

explanation of the procedures to obtain a

CLIA certificate is available at 

https://www.cms.gov/Regulations-andGuidance/Legislation/CLIA/downloads/

HowObtainCertificateofWaiver.pdf. 

•		State regulatory issues. Many States

have their own regulations regarding POCTs

that practitioners or their designees must

learn before they start to test. 

Cost. The information on the economics 

of POCT for drugs and ethanol is limited,

although cost issues should be important in 

deciding to initiate a point-of-care drug-testing

program. The fixed unit price of POCTs

often exceeds those of laboratory-based test

methods. However, the cost of devices also 

depends in large part on the number of drugs

included in the test panel, the difficulty

in identifying the substances included in

the panel, the number of devices ordered,

and the volume of testing. Costs may vary

according to location. In general, as the

demand for POCTs grows, the cost per

device decreases. In addition, the extra staff 

time and space to perform the test, staff

training, quality assurance procedures, and

documentation need to be taken into account 

when considering the cost. Then again, staff

already collect specimens and perform POCTs

to test for other conditions in many physician

practices. These costs should be carefully

reviewed prior to initiating POCT for drug

testing. 
29 

Chapter 3―Preparing for Drug Testing

Other Considerations. Practitioners should 

research the point-of-care devices being

considered for use in terms of (Melanson,

2005): 

•		Analytic performance. Seemingly minor

differences in sensitivity, specificity, and

accuracy among the available POCT

devices may or may not be clinically

important and must be evaluated. 

•		Cross-reactivity. Some devices may

not be able to distinguish between the

substance being tested for and other

chemically similar substances. 

•		Validation studies. Lot-specific evaluation

information is usually summarized in

package inserts, with more extensive

verification documentation available on 

request. A POCT manufacturer may have

additional credentials documenting that

the testing device and the manufacturing

processes meet quality control and quality

assurance standards (e.g., certification

by the International Organization for

Standardization). 

•		Ease of use. Most POCT devices can 

be operated by an individual with little

laboratory experience. However, some

devices may entail following fairly complex

instructions for use, which can contribute 

to human errors that will affect test 

results. Even test operators with technical

or scientific backgrounds can make errors

using these devices because of lack of

training or unfamiliarity with new devices. 

•		Ease of reading and interpreting

the results. Most devices require visual

interpretation of a color response. Clear,

distinguishable results are necessary

for accurate interpretation. It is also

necessary to know which substances will

cross-react and produce a false-positive

result (e.g., pseudoephedrine giving

an “amphetamines” positive) or a false 

negative result (e.g., oxycodone and its

active metabolite oxymorphone, both

of which are opiates, giving a negative

opiates result when either or both are

present in the patient’s specimen). 

•		Quality assurance and control

procedures. Devices differ in the amount 

of time needed for staff to learn quality

control procedures, such as completing

documentation to ensure adherence 

to the manufacturer’s instructions for 

maintenance (if any) and assay of the

appropriate control specimens at the

required intervals. Maintenance and

quality control procedures also must meet

CLIA, State, and local regulations. Positive

and negative quality control samples must

be included to verify accurate testing, but

the frequency of analysis of quality control

is dependent upon State regulations or

regulatory agency. 

•		Laboratory testing for verification. 

It is suggested that a percentage (i.e., 5

percent) of specimens that screen negative

or positive be sent to a laboratory to verify

accurate performance of POCT results, and

that all positive results that are contested

by patients be submitted to a laboratory

for confirmation testing. 

Implementing Point-of-Care Testing 

Based on surveys of sites holding CLIA

waivers, Howerton, Anderson, Bosse, 

Granade, and Westbrook (2005) suggest that

practitioners consider the following questions

when deciding whether to use any type of

POCT device: 

• Who will manage and be accountable for 

testing oversight? Can this person receive

the appropriate training? 

• Are there sufficient personnel to conduct

testing? 

• How will testing affect workflow? 

•		How will staff be trained to conduct a 

POCT? 

•		Can the site adequately comply with

Federal, State, and local regulations

regarding the POCT? 

• What are the safety considerations for both

personnel and patients? 
Clinical Drug Testing in Primary Care

30 

•		Can personnel reasonably follow quality

control procedures? 

•		Does the site meet physical requirements

for testing (e.g., space for collection,

testing, storage, security)? 

• What are the benefits and costs of POCTs 

to the practitioner? 

•		How will testing records be maintained?

What written documentation is needed? 

• What are the plans for quality control

testing and quality assurance? 

Preparing Clinical and Office Staffs for 

Testing 

Once a practitioner has decided which

matrices and types of tests to use, the clinical

and office staffs need to be prepared to begin

testing. Preparation may include: 

•		Obtaining a CLIA waiver; 

•		Developing written policies and procedures

for testing, including ongoing staff

training, and establishing quality control

procedures; 

•		Developing and implementing testing

protocols, including guidelines for

specimen collection, use of POCT,

confirmatory testing, and laboratory

technical assistance; 

• Establishing confidentiality safeguards; 

•		Training staff in use of the selected POCT

devices and in collecting specimens for

laboratory testing; 

•		Establishing recordkeeping procedures; 

•		Preparing appropriate storage sites for

completed POCTs and laboratory tests;

and 

•		Arranging pickup or transportation for

laboratory tests. 

Preparing a Specimen Collection 

Site 

The collection site is a designated area where

a patient provides the specimen for a drug

test. Collection of most specimen matrices

does not require special arrangements. Urine

collection in primary care settings needs

to be configured for privacy while a patient

provides a specimen if direct observations

are not required. Water for drinking needs to

be available in the event the patient cannot

provide sufficient urine (shy bladder). In

substance abuse treatment and workplace

testing, measures need to be taken to prevent

adulteration or substitution, such as putting

a bluing agent in the toilet, not providing

access to soap and water in the collection

room, and directly observing specimen

provision. These actions are needed in clinical

situations only if adulteration or substitution

is suspected. Once specimens are collected

and labeled, there must be space and proper

conditions for securely and appropriately

storing them. A refrigerator is a convenient,

appropriate storage place, especially when

samples are picked up by a laboratory courier

on a daily or less frequent basis. 
31 

Chapter 4—Drug Testing in Primary Care
 

In This Chapter 

•		 Uses of Drug Testing

in Primary Care 

•		 Talking With Patients

About Drug Testing 

•		 Cultural Competency

and Diversity 

•		 Monitoring Patients 

•		 Ensuring

Confidentiality and 42

CFR Part 2 

•		 Preparing for

Implementing Drug

Testing 

•		 Interpreting Drug

Test Results 

•		 Frequency of Testing 

•		 Documentation and 

Reimbursement 

Uses of Drug Testing in Primary Care 

Primary care providers order a wide array of laboratory tests

as part of routine physicals and to determine the cause of

symptoms, adjust medication dosages, monitor treatment

effectiveness, and diagnose. Drug tests can be ordered and

used for these same reasons. 

Discussing substance use with patients can be time-consuming

and may upset some patients. However, if a drug test is

indicated, talking with patients before, after, and even if drug

testing is refused can yield information that may improve

many aspects of primary care. Some examples of when the

use of drug testing or discussing substance use could improve

patient care include: 

•		Evaluating unexplained symptoms or unexpected responses

to treatment and identifying substance use that has

contributed to, caused, or is complicating the patient’s 

treatment; 

•		Evaluating patients in psychiatric care for substance abuse 

issues, or before prescribing psychoactive medications; 

•		 Identifying potential substance use problems in women

who are pregnant, or planning on becoming pregnant, and

identifying at-risk neonates; 

•		 Identifying patients with possible substance abuse issues; 

•		Monitoring patients in substance abuse treatment: to

assess the efficacy of the treatment plan and the level

of care, to monitor abstinence before administering

medications to treat substance use disorders (SUDs),

and to help identify a relapse to substance use; 

•		Ensuring patient safety prior to surgery or other invasive

procedures to prevent medication interactions; 

•		Managing patients prescribed opioids for chronic pain

control; and 

•		Monitoring potentially addictive prescription use (e.g.,

sedatives, tranquilizers, medications to treat attentiondeficit/hyperactivity disorder [ADHD]). 
Clinical Drug Testing in Primary Care

32 

Monitoring Prescription Medication Use 

Drug testing is useful for monitoring patient

treatment compliance with prescribed

medications that have addictive properties

(e.g., opioid pain medication, sedatives,

ADHD medication). Test results can reveal

whether patients have recently taken their

prescribed medication and if non-prescribed

or illicit drugs have been used. Drug testing

can help practitioners identify and reduce

diversion of scheduled drugs by patients. 

Management of Chronic Pain With Opioids 

Primary care practitioners often provide

medical management for patients taking

opioids for chronic pain. Long-term pain

treatment with opioids requires monitoring

for continuing effectiveness for pain relief

and the potential for misuse, addiction,

or diversion. Current clinical guidelines

recommend the use of drug tests for pain

management with opioids to help guide

decisions about prescribing scheduled

medications, revising treatment regimens,

and when to initiate or refer for substance 

abuse treatment (Chou et al., 2009; Fishman,

2007). 

Gourlay, Caplan, and Heit (2010) suggest

that drug testing may be useful for: 

•		New patients as part of regular care to

indentify the use of illicit or nonprescribed

drugs; 

•		Patients being prescribed a controlled

substance; 

•		Patients who present with a condition that

warrants a prescription for a controlled

substance and who resist a full evaluation 

or who request a specific medication with

addictive potential; 

•		Patients with aberrant behavior 

(e.g., patients who consistently want

appointments toward the end of office

hours, arrive after office hours, insist on 

being seen immediately, repeatedly report

losing prescriptions or medications, are

reluctant to change medication, do not

adhere to the treatment plan); 

•		Patients who are suspected of diversion; 

•		Patients who need advocacy to verify their

abstinence; 

•		Patients in recovery from SUDs; and 

•		Patients who need a change in their 

treatment. 

Katz and colleagues (2003) conducted a

3-year study on behavioral monitoring and

urine drug testing in patients receiving

long-term opioid therapy for pain. Their

findings suggest that random drug testing

of all patients receiving opioids for pain

may be warranted. The researchers found

that urine drug testing was much more

effective than behavioral monitoring alone

in identifying patients who were taking

drugs other than the prescribed opioid.

For example, 72 percent of patients with

a positive test result did not have any

behavioral indicators considered useful for 

screening. 

Evaluation of Unexplained Symptoms or 

Unexpected Responses to Treatment 

The results of drug tests can clarify situations

in which substance use contributes to, causes, 

or complicates diagnosis or treatment, but the

substance use is not apparent to the clinician.

Patients may not disclose: 

•		All the medications prescribed by other

providers or over-the-counter (OTC)

medications and herbal products; 

•		That they take medications prescribed for

other people; 

•		Use of illicit drugs or how much alcohol

they consume; or 

•		 If they have stopped taking their

medications. 
33 

Chapter 4—Drug Testing in Primary Care

 

 

Following are some clinical examples of when

or where drug testing might explain the

cause of symptoms or unexpected response to 

treatment: 

•		A man whose hypertension remains

uncontrolled, despite adhering to a

low-salt diet and several antihypertensive

medication changes, who does not inform

the clinician that he drinks more than four 

drinks almost every evening and more on

weekends. 

•		A college student who complains of heart

palpitations, but does not mention using

her roommate’s medication for ADHD to 

help her study. 

•		An elderly woman who is increasingly

confused and somnolent and has a normal 

physical, tests, and laboratory results, but

does not state that she self-medicates with 

her friend’s prescribed benzodiazepines to

help her “nerves.” 

•		A patient with pancreatitis who repeatedly

denies alcohol use and is negative for any

other causes. 

In clinical situations, such as these and others, 

practitioners can order drug tests and use the

results to gain a better understanding of the

true clinical picture, determine the diagnosis,

talk to the patient, and then work more

effectively with the patient. 

Patient Safety 

In some cases, ensuring patient safety is

the primary reason for testing in clinical

situations. For example: 

•		Preoperative or preprocedure

evaluations. Primary care providers

often do evaluations for their patients

prior to planned surgery or other invasive

procedures. Drug tests may identify

medication or illicit drug use not disclosed

during the practitioner–patient interview.

Drug testing can be used if the practitioner

suspects that the patient is using drugs,

or if the patient has a history of drug use.

The primary care physician can alert the 

anesthesiologists or radiologists to the

possible presence of substances that could

cause adverse drug reactions, interfere

with anesthesia, prevent possible cardiac

complications or respiratory depression,

prevent the patient from experiencing

withdrawal if hospitalized, or experience

poor pain management if the patient has

been taking high doses of opioids and has 

developed tolerance. 

•		Preventing toxic drug interactions .

Drug testing may reveal a patient’s use of

multiple substances, both legal (prescribed

and OTC medications) and illicit drugs. A

practitioner needs this information before

prescribing a new medication or starting

pharmacotherapy for SUDs, psychiatric

conditions, and other health problems. For

example, a toxic interaction can occur if a

patient uses other central nervous system

depressants while taking buprenorphine or

methadone. 

Pregnancy 

Drug and alcohol testing of women who are

pregnant or who want to become pregnant

is an opportunity to prevent damage to the

woman and the fetus. During preconception

counseling, women should be advised about

the risks of alcohol, tobacco, and drug use to

the fetus. Screening for substance use should

be done so that the patient can be assessed

and referred to treatment before becoming

pregnant. SUD screening and assessment of

a pregnant woman can identify an SUD early

enough for intervention and for preventing,

minimizing, or at the very least preparing

for serious problems for the fetus or neonate.

Pregnant women should be strongly urged

to abstain from alcohol and drugs, and, if

necessary, referred to treatment as soon as

possible. Drug testing can be used to monitor

abstinence. 

A difficult dilemma is created by State laws

that require the reporting of nonmedical

use of controlled substances by a pregnant

woman or that require drug testing after

delivery if illicit drug use is suspected.

These laws can have the unintended effect 
Clinical Drug Testing in Primary Care

34 

of women not seeking prenatal care. Drug

testing during pregnancy, or postnatally,

can have severe consequences. In many

States, pregnant and parenting women

can be reported to child protective services,

even though the courts have struck down

criminal charges against women who are

pregnant and use drugs. Women have the

right to refuse drug testing (American College

of Obstetricians and Gynecologists, 2008);

however, if drug abuse is suspected that is

contributing to child abuse, reporting to child

protective services is necessary. 

Psychiatric Care 

Drug testing is uncommon for patients

who are primarily being treated for mental

disorders, but should be considered when 

assessing a patient presenting with mood or

behavior changes (Black & Andreasen, 2011).

Drug tests could be used with patients with

possible mental disorders to aid in diagnosis,

help determine whether the psychiatric

symptoms are substance use or withdrawal

related, or to identify a co-occurring SUD. 

Controlled substances are prescribed for some

psychiatric conditions (e.g., benzodiazepines

for chronic anxiety disorder or stimulants for

ADHD). Drug test monitoring for adherence

to controlled medications may be indicated

for some patients. 

Monitoring Office-Based Pharmacotherapy 

for Opioid Use Disorders 

The Drug Addiction Treatment Act of 2000

(DATA 2000) permits office-based substance

abuse treatment by allowing certified

physicians to prescribe Schedule III, IV, and

V medications to treat opioid dependence. To

prescribe buprenorphine, a Schedule III

opioid medication, physicians must qualify

for a DATA 2000 waiver. Physicians

providing office-based pharmacotherapy use

drug testing to monitor compliance with

pharmacotherapy and abstinence from illicit

opioids. For more information, visit http://

buprenorphine.samhsa.gov/index.html

and see Treatment Improvement Protocol 

(TIP) 40: Clinical Guidelines for the Use of 

Buprenorphine in the Treatment of Opioid 

Addiction (Center for Substance Abuse

Treatment [CSAT], 2004). 

Detection of Substance Use Disorders 

Many patients seeing primary care providers

have an undiagnosed SUD and providers can

play important, preventive roles in detecting

and addressing SUDs in the primary care

setting. Drug testing can aid the provider

in identifying those patients using illicit

substances and screen them further for a 

possible SUD. It must be noted that a positive

drug screen is not diagnostic in itself of an

SUD. 

The practitioner can find clues for a possible

SUD in a patient’s laboratory findings,

physical examination, and medical history.

For example, liver enzyme abnormalities may

suggest current or past alcohol misuse or

dependence, and hepatitis B and C antibodies

can suggest current or past drug use. A

physical examination may reveal track marks

or abscesses, or a patient may have a history

of medical conditions that suggests an SUD

(e.g., cirrhosis, pancreatitis). Other physical

signs include frequent falls or injuries,

bruises the patient cannot explain, physical

complaints without corresponding physical

findings, deterioration in personal hygiene,

and disheveled appearance. 

Physical signs of SUDs may not appear

until late in the progression of the disorder.

Nonphysical or behavioral signs could

include: 

•		Reports of marital, academic, or

employment problems; 

•		Chaotic lifestyle; 

•		Deterioration in grooming or hygiene; 

•		Unusual mood swings or outbursts; 

•		Money or other valuable items missing

from the home; 
35 

Chapter 4—Drug Testing in Primary Care

• Requests for specific potentially addictive

medications; and 

•		Frequent reports of losing prescriptions

for potentially addictive medications. 

Initial Assessment of a Person With a 

Suspected SUD 

A positive drug test does not necessarily

indicate a diagnosis of an SUD. The drug use

could be sporadic and not meet the diagnostic

criteria in the Diagnostic and Statistical 

Manual of Mental Disorders, Fourth Edition, 

Text Revision (American Psychiatric

Association, 2000). These patients will need

screening and assessment. When informing

a patient about the test results of an initial

assessment, the practitioner can: 

•		 Inform the patient about the health and

medical consequences (Fleming, 1995).

Once screening results are explained,

describe the health risks and medical 

consequences of use of the substance

in question. For some (e.g., people with

chronic hepatitis) any consumption of a

substance, such as ethanol, may be unsafe.

Likewise, the use of stimulants, such as 

cocaine and amphetamines, could have

disastrous consequences for a patient

with compromised cardiac function or

hypertension. Women who are pregnant

or who want to become pregnant should

be told of the dangers an SUD poses to

the fetus and the mother, receive further 

assessment, or be referred to SUD 

treatment. 

•		Pay careful attention to semantics.

Avoid pejorative labels of “alcoholic” or

“addict.” Use neutral, nonstigmatizing

language (e.g., “people with substance

use problems”). Do not use humiliating or

confrontational approaches to try to force

the patient to agree to treatment. 

• Recognize that a positive test result may

trigger patient resistance or feelings of

guilt, shame, or anger. Avoid arguing

with the patient. Negative reactions can

often be countered by focusing on the 

relationship between the original health

complaint and the patient’s use of drugs or

alcohol. 

•		Demonstrate an understanding and

acceptance of the patient and communicate

that the clinician will help the client help

himself or herself. 

•		Address goals and strategies for change.

Assess the patient’s readiness for change.

Help the client clarify the nature of his

or her difficulties. Express empathy and

a willingness to listen to the client. Use

motivational counseling approaches to

encourage further screening or assessment

or treatment options. Foster hope for

positive change. Resources for more

information about motivational approaches

are in Exhibit 4-1. 

A positive test result for illicit drugs or

nonprescribed licit medications does not

necessarily mean that the patient has an

SUD; it means that the SUD may exist and

the patient needs further screening to rule

out an SUD or determine whether an SUD 

assessment is needed. The practitioner can

do brief office-based screening, using the test

result to start a discussion. The practitioner

can also use a screening instrument; the

simplest and quickest screening instrument

is CAGE-AID (Exhibit 4-2). CAGE-AID is a

tool that has been tested with primary care

patients (Brown & Rounds, 1995). 

Exhibit 4-1. Motivational Interviewing 


Resources
 

•	TIP 35: Enhancing Motivation for Change in 


Substance Abuse Treatment (CSAT, 1999b)
 

•	KAP Keys for Clinicians Based on TIP 35 

(CSAT, 2001a) 

•	 Quick Guide for Clinicians Based on TIP 35 

(CSAT, 2001b) 

•	Motivational Interviewing: Preparing People 

for Change (Miller & Rollnick, 2002) 

•	The Motivational Interviewing Page 


(http://www.motivationalinterview.org)
 

•	Helping Patients Who Drink Too Much: A 


Clinician’s Guide, Updated 2005 Edition 


(National Institute on Alcohol Abuse and 

Alcoholism, 2007) 
Clinical Drug Testing in Primary Care

36 

Exhibit 4-2. The CAGE-AID Questions 

1.Have you felt you ought to Cut down on your 

drinking or drug use? 

2.Have people Annoyed you by criticizing your 

drinking or drug use? 

3.Have you felt bad or Guilty about your 


drinking or drug use? 


4.Have you ever had a drink or used drugs first 

thing in the morning to steady your nerves or 

to get rid of a hangover (Eye-opener)? 

The National Institute of Drug Abuse’s

(NIDA’s) NIDAMED provides resources for

health professionals and is available at http://

www.nida.nih.gov/nidamed/screening/. 

The NIDAMED Web site includes a number 

of resources, such as: 

• NIDA’s Clinician’s Screening Tool,

NIDA-Modified Alcohol, Smoking, and

Substance Involvement Screening Test

(NMASSIST), is available online and in

hard copy. 

•		Resource Guide: Screening for Drug Use

in General Medical Settings provides

information on using the 5As–Ask, Advise,

Assess, Assist, and Arrange. 

NMASSIST is a well-validated tool in general

medical settings. The empirical evidence is

good for screening and brief intervention for

alcohol use disorders in a primary care

setting, but it is more limited for the treatment

of drug use disorders, which might require a

more intensive care setting. 

Several screening and assessment tools

are listed in Appendix C—Screening and

Assessment Instruments in TIP 24: A Guide 

to Substance Abuse Services for Primary Care 

Clinicians (CSAT, 1997). 

When screening or a brief assessment

indicates a problem with substance use,

the practitioner may want to try brief

office-based interventions. A brief 

intervention is a pretreatment tool or

prevention technique that involves 

office-based, practitioner-patient contacts

of 10–15 minutes for a limited number 

of sessions. The number and frequency

of sessions depend on the severity of the

problem and the patient’s response. A brief

intervention can be useful before or after 

an indepth assessment and both during

and after specialized treatment as part of

followup and relapse prevention. Exhibit 4-3

lists basic elements of brief interventions 

using FRAMES. More indepth information

can be found in TIP 34: Brief Interventions 

and Brief Therapies for Substance Abuse

(CSAT, 1999a); TIP 24: A Guide to Substance 

Abuse Services for Primary Care Clinicians

(CSAT, 1997); Brief Intervention for 

Hazardous and Harmful Drinking: A Manual 

for Use in Primary Care (Babor & HigginsBiddle, 2001); and at the Substance Abuse

and Mental Health Services Administration’s 

(SAMHSA’s) Web site on screening, brief

intervention, and referral to treatment http://

www.samhsa.gov/prevention/SBIRT/index. 

aspx. 

Exhibit 4-3. Brief Intervention Elements: 


FRAMES
 

Feedback—The practitioner gives patients 

personalized feedback relevant to their 

individual situation. 

Responsibility—The practitioner lets patients 

know that they are ultimately responsible for 

their recovery. 

Advice—Studies have proved that even brief 

sessions providing information or advice about 

substance use can lead to behavior changes 

(Rollnick, Heather, & Bell, 1992). 

Menu—Giving patients a menu of strategies (as 

appropriate to the treatment situation) adds to 

the sense of responsibility patients feel. 

Empathy—An empathetic approach to 

treatment has been positively linked to positive 

treatment outcomes. 

Self-Efficacy—The feeling of self-efficacy (e.g., I 

can change) is critical to promoting behavioral 

changes in patients. Patients’ belief that they 

are capable of changing their behavior can help 

them through challenging parts of recovery. 

Source: Miller & Sanchez (1994) 
37 

Chapter 4—Drug Testing in Primary Care

If a practitioner suspects an SUD, he or 

she can refer the patient to appropriate 

psychosocial or medication-assisted treatment 

services. Often, making a telephone call to 

a treatment facility while the patient is in 

the office is the best way to get a patient 

to treatment. Substance abuse treatment 

providers will do a thorough assessment and 

recommend the least intensive environment 

that is safe and effective for the patient. 

The practitioner should follow the patient’s

progress in treatment and request evidence

of the patient’s adherence to prescribed

psychosocial services. Brief interventions can

be successful. The patient could also have

drug tests during subsequent visits to assess

progress. Exhibit 4-4 provides a flowchart of

the screening, assessment, brief intervention,

and referral processes in primary care

settings. 

Exhibit 4-4. Patient Flow Through Screening and Referral in Primary Care 
Clinical Drug Testing in Primary Care

38 

For more information, refer to the following

publications: 

•		TIP 24: A Guide to Substance Abuse 

Services for Primary Care Clinicians

(CSAT, 1997) 

•		TIP 40: Clinical Guidelines for the Use of 

Buprenorphine in the Treatment of Opioid 

Addiction (CSAT, 2004) 

•		TIP 49: Incorporating Alcohol 

Pharmacotherapies Into Medical Practice

(CSAT, 2009) 

•		Screening for Drug Use in General Medical 

Settings, Quick Reference Guide (NIDA,

2009) 

•		Helping Patients Who Drink Too Much: A 

Clinician’s Guide (National Institute on

Alcohol Abuse and Alcoholism, 2007) 

Talking With Patients About Drug 

Testing 

Prior to testing, important tasks for the

practitioner are to explain to patients: (1) the

reasons for performing drug testing, (2) use

of the test results, and (3) the practitioner’s

duty to maintain confidentiality. It should

also be explained to the patient that the

drug tests and the results will become

part of the patient’s record. Establishing a

trusting relationship in which patients feel

comfortable about confiding substance use

helps address any questions or negative

reactions to testing or test results. If the

patient has language, hearing, or

vision-related challenges, accommodations

may need to be made with the use of a

translator or assist technologies. Key

practitioner actions that contribute to

such a relationship include: 

•		Communicating openly; 

•		Having an understanding attitude; 

•		Listening actively; 

•		Treating the patient with dignity

and respect; 

•		Reassuring the patient regarding

confidentiality of medical records; 

•		Having a straightforward, but

nonjudgmental attitude; and 

•		Using a matter-of-fact, nonconfrontational

approach in explaining the reasons for

drug testing and any subsequent treatment. 

Explicit consent for drug testing is not

required in primary care settings. However,

there are reasons why practitioners should

inform patients before drug testing: 

•		The practitioner–patient relationship. 

Although patients may assume they will

be tested for cholesterol or glucose levels,

most do not expect to be tested for drug

use. Patients confronted with results 

of tests that they did not realize were

being performed may feel betrayed by

the practitioner, possibly eliminating the

chance for discussion about substance 

use problems and harming the

practitioner–patient relationship. 

•		Privacy. If the practitioner orders a test

and the cost is submitted to the insurance 

company, the patient’s health insurance

company will know about it. Patients

should have the choice of deciding whether

they are willing to have their insurance

carrier learn this information. 

•		Reimbursement. Patients’ third-party

payers may not cover drug tests. If

insurance companies do not pay for the

test, patients should decide whether

they are willing to self-pay; this decision

should be made before the test is done. 

The patient may want to pay out of pocket

to keep the drug test out of his or her

insurance record. 

Before testing, the practitioner needs to

emphasize to patients the importance of

revealing all prescription and nonprescription

drugs (including OTC medications and herbal

preparations) they are taking. Patients may

not realize that OTC or herbal products can

affect drug test results. 
39 

Chapter 4—Drug Testing in Primary Care

Even if a patient refuses to consent to a

drug test, the conversation between the

practitioner and patient may facilitate a

discussion about possible substance use

problems. The practitioner could begin by

asking why the patient does not want to

have a drug test, or agree to re-visit the issue

during another visit. A patient may be willing

to examine his or her behavior after refusing

the test. 

Discussing drug testing results can be

difficult. Patients need clear and thoughtful

explanations of the test results and the terms

positive, negative, adulterated, dilute, or

substituted. They need to understand why

the test was positive or negative and what

that means for the patient and any treatment.

All results should be presented in a

straightforward, nonjudgmental manner

using terms the patient understands.

Effective communication is essential for 

the practitioner–patient relationship to be

successful in these circumstances. 

Cultural Competency and Diversity 

The ease or difficulty in establishing and

maintaining a therapeutic alliance is affected

by many factors, including the amount

of time the practitioner can spend with

the patient, the backgrounds of both the

practitioner and the patient, the patient’s

ability to speak English, and acculturation

levels (if the patient is from another country).

Drug testing with some patients from diverse

groups can be challenging due to their

cultural beliefs, history, and heritage. Some

patients may distrust the medical profession

because of past abuses by the medical

community. They might feel additional shame 

about SUDs because of the strong stigma in

their community, they might fear disclosure

to law enforcement, or they might possess

a different idea of what constitutes normal 

drinking versus problematic drinking. 

Some approaches to help improve

communication in these circumstances 

include: 

•		Providing an explanation of the

practitioner’s perceptions of the problem

and listening, with sympathy and

understanding, to the patient’s perception

of the problem. 

•		Acknowledging and discussing the

differences and similarities in beliefs about 

treatment. 

•		Recommending treatment and then

negotiating a treatment agreement (Berlin

& Fowkes, 1983). 

Following are some ideas for the practitioner

to consider when treating patients from

diverse backgrounds: 

• Culture is important in every patient’s

identity. 

•		Communication of cultural understanding

and respect is essential for establishing 

rapport. 

•		Culture-related stresses and tensions can 

induce illness. 

•		Culture-related behaviors or beliefs (e.g.,

religion, family structure and influence,

health practices, traditional health

beliefs) affect patients’ acceptance of and

compliance with prescribed therapy. 

•		Nonverbal and verbal communication may

differ from culture to culture. 

•		Customs and attitudes surrounding SUDs

may differ from the accepted medical

definition. 

•		Awareness of prevailing cross-cultural

tensions and psychosocial issues may help

the practitioner understand patients from

that culture (Bobo, Womeodu, & Knox,

1991). 
Clinical Drug Testing in Primary Care

40 

Intercultural skills need to be as specific as

possible for each culture. For example, the

practitioner should: 

• Attempt to understand how the patient’s

background and culture can affect 

treatment. 

• Elicit the patient’s understanding of drug

testing. 

•		Negotiate a culturally relevant care plan

with the patient as partner. 

•		 Interpret verbal and nonverbal behaviors

in a culturally relevant manner. 

• Acknowledge the patient’s role as an active

participant in his or her own care (Bobo et

al., 1991). 

Monitoring Patients 

Patients With an SUD 

If the practitioner is providing substance

abuse treatment, drug testing can: 

•		Objectively monitor abstinence from drugs

or alcohol; 

•		Monitor response to treatment; 

•		Corroborate self-reports; 

•		Help address denials of substance use; and 

•		 Identify relapse to substance use. 

For example, an increasing number of

physicians provide medications for alcohol

use disorders (e.g., disulfiram, naltrexone).

Drug testing can be used to help monitor

patients’ use of drugs, if necessary, and

is needed before starting naltrexone. The

patient and practitioner need to negotiate

a plan of action to address the patient’s

substance use and monitor progress. Any

medical problem other than substance

use (e.g., hypertension) should also be

monitored, as should any abnormal biological

markers (e.g., elevated gamma-glutamyl

transpeptidase levels in patients who abuse

alcohol). 

A practitioner using drug tests may seem

intrusive to some patients, whereas other

patients welcome the discipline imposed.

The practitioner and patient should

negotiate the use of any form of objective

monitoring beyond self-reports of substance

use. Biological monitoring should be viewed

as an informative measure, not cause for 

punitive action against the patient. Repeated

positive urine drug test results mean that

the treatment plan is not working and that

another approach should be considered.

Efforts to reduce the patient’s substance use

by monitoring drug test results work best

in conjunction with open communication

between the practitioner and the patient. 

Monitoring treatment compliance is a

trust issue, and trust is important for the

development of the therapeutic alliance. The

practitioner needs to create an environment

in which the patient feels safe to report

honestly how he or she is progressing in

recovery. Relapses are a normal part of the

natural history of recovery, and how the

practitioner responds to them is essential

to building a therapeutic alliance and trust.

Getting honest with oneself and others about

one’s substance use and its impact on one’s

life is essential to lasting recovery, so honesty

is an important ground rule for establishing

the patient–practitioner relationship. That

said, the practitioner should be clear early

on that addiction leads some patients to be

dishonest about their drug use, so a policy of

“trust yet verify” is used—drug testing and

corroboration from family can help verify

the patient’s reports. The practitioner should

express trust in the patient; then, if the

patient is not honest about reporting

substance use, the practitioner must address

the lack of honesty as a therapeutic issue that

impedes recovery. If a patient tries to deceive

the practitioner, the practitioner should be

direct yet empathic: “I know it is hard to stop

using. What do you think might help?” 

The response to a positive drug screen in

patients being treated for an SUD depends

on more than one factor, including the types

of drugs found in the test. If positive results 
41 

Chapter 4—Drug Testing in Primary Care

continue and the patient is not progressing,

the patient may need referral to more

intensive treatment. However, if the patient

readily admits to a relapse and seems fully

committed to continuing treatment, the

practitioner should support the patient’s

recommitment to recovery. Each patient

needs to be assessed as an individual. If 

the patient is receiving medication-assisted

treatment, the dosage may need to be

increased. 

An important concept of substance abuse

treatment is that one failure (e.g., relapse,

leaving treatment), or even multiple

treatment failures, is not a reason to 

deny further treatment to a patient. The

practitioner should expect relapses and be

prepared to respond in a therapeutically

appropriate manner. The patient may not be

able to achieve recovery after one, or even

several, treatment periods. SUDs are chronic,

relapsing conditions that often need repeated

interventions or treatments before a patient

is stabilized. The practitioner should not

expect that patients with problems related

to alcohol and drug use will have any less

difficulty than other patients in making

significant lifestyle changes. 

Unless a practitioner is testing for all

substances (which is virtually impossible),

heavy reliance on drug tests can be

misleading in monitoring abstinence.

Patients can abstain from their substance 

of choice while using other substances that

may not be part of a particular drug test

panel. Practitioners should test not only for

the patient’s substance of choice, but also

other commonly abused drugs. In general,

the practitioner should avoid using drug

testing as a punitive measure. A cooperative

practitioner–patient relationship includes

trusting the patient’s self-report of substance

use, with drug testing used to verify reports. 

If a patient is currently in treatment for

substance abuse at a treatment center, he or 

she is likely being tested for drug use. In this

case, it is cost effective—and in the patient’s

best interest—for the practitioner to ask the 

treatment program (with permission from the

patient) for drug test results rather than to

repeat a drug test. 

Monitoring Patients Receiving Opioids for 

Chronic Noncancer Pain 

Urine drug tests are becoming more common

to monitor patients receiving chronic opioid

analgesics. In pain management, drug tests

can be useful, but they need to be used

thoughtfully. The plan and reasoning for

drug testing for these patients needs to be

discussed thoroughly with the patient. Some

patients may find drug tests intrusive; others

accept the practice. Drug tests tend to be

associated with drug abuse treatment and

some patients may be offended when asked

to participate in drug testing as part of pain 

treatment. 

Drug tests do not monitor therapeutic drug

levels; they provide information regarding

medication adherence to the prescribed

medication and/or the ingestion of illicit

drugs. The only exception is the use of serum

methadone levels. If the drug test shows

the use of illicit drugs in addition to the

prescribed medications, the patient needs to

be educated regarding the danger of using

illicit substances and opioid pain medications

and that substance abuse is not helpful to

long-term pain management. Some patients

may need to be referred to specialists in both

addiction and pain management. 

To properly interpret urine drug screens, a

detailed understanding of the pharmacology

of the prescribed opioid and its relationship

to the urine-testing technique must be

understood by the prescribing provider. A

negative test result when a positive one

was expected (e.g., pain medication) may

also trigger patient resistance or feelings of

guilt, shame, or anger. In these cases, it is

important that the practitioner avoid arguing

with the patient and remain nonjudgmental.

For more information, see TIP 54: Managing 

Chronic Pain in Adults With or in Recovery 

From Substance Use Disorders (SAMHSA,

2012). 
Clinical Drug Testing in Primary Care

42 

Ensuring Confidentiality and 42 

CFR Part 2 

The concern about the adverse effects 

that negative attitudes about SUDs

and discrimination have on patients in

recovery—and how those adverse effects

might deter people from entering

treatment—led the U.S. Congress to pass

legislation and the Department of Health

and Human Services (HHS) to issue a

set of regulations to protect information

about patients’ substance abuse. The law is

codified at 42 United States Code §290dd2. The implementing Federal regulations,

“Confidentiality of Alcohol and Drug Abuse

Patient Records,” are contained in 42 

CFR Part 2 (Vol. 42 of the Code of Federal

Regulations, Part 2). The law and regulations

severely restrict communications about

identifiable patients by “programs” providing

substance use diagnosis, treatment, or

referral for treatment (42 CFR §2.11). These

rules are stricter than the general Health

Insurance Portability and Accountability Act

of 1996 (HIPAA) rules about disclosure of

personal health information. Under HIPAA,

information can be disclosed without written 

consent for the purposes of routine clinical

care and most administrative functions. 

Written permission from the patients for

these disclosures is generally required by 42

CFR Part 2. 

In most primary care settings, 42 CFR Part

2 does not apply. Confusion persists about

whether general medical care settings (e.g.,

primary care clinics, hospital emergency

rooms) are subject to the law and related

regulations because they provide substance

abuse diagnosis, referral, and treatment as

part of their services. In 1995, HHS revised

the definition of the kinds of programs

subject to the regulations, clarifying that the

regulations do not usually apply to a general

medical care facility unless that facility (or

person) “holds itself out as providing, and

provides, alcohol or drug abuse diagnosis,

treatment or referral for treatment” (42 CFR

§2.11). 

Practitioners should be aware that if a 

healthcare practice includes someone whose

primary function is to provide substance

abuse assessment or treatment, and if the 

practice benefits from Federal assistance

(including Medicare or Medicaid payments),

that practice must comply with the 42 CFR

Part 2 law and regulations and implement

special rules for handling information about

patients who may have substance abuse

problems (CSAT, 1997). Clinicians who use a

controlled substance (e.g., benzodiazepines,

methadone, buprenorphine) for detoxification

or maintenance treatment of an SUD are 

also subject to this regulation. However,

physicians who do not use a controlled

substance for treatment (e.g., naltrexone) are

not subject to the regulation (SAMHSA, n.d.). 

In practices subject to 42 CFR Part 2, the

results of a patient’s drug test and substance

use history are confidential and may not be

revealed to a third party without the patient’s

consent, except in certain circumstances (e.g.,

if the patient was mandated to treatment).

Patients must be told before being tested

whether the test results must be reported. In

addition, any releases of information must

specify that the information cannot be shared

with a third party without specific consent of

the patient. 

Many States offer additional protection

to medical information about patients

that is as strict or stricter than 42 CFR 

Part 2. However, each State has its own 

set of rules, which means that the scope

of protection offered by State law varies.

Whether a laboratory test result is privileged

or protected information may depend upon

several factors: 

•		The type of professional holding the

information and whether he or she is 

licensed or certified by the State; 

•		The context in which the information was 

communicated; 

•		The context in which the information will 

be or was disclosed; and 

•		Exceptions to any general rule protecting

information. 
43 

Chapter 4—Drug Testing in Primary Care

Which practitioners are covered depends on

the State within which the clinician practices.

Practitioners should consult with their 

State medical or substance abuse treatment 

authorities to ascertain the requirements and

regulations in their State. SAMHSA provides

a directory of State agencies for substance

abuse services located at http://www.samhsa.

gov/Grants/ssadirectory.pdf. 

For more information, see Appendix B of TIP

24: A Guide to Substance Abuse Services for 

Primary Care Clinicians (CSAT, 1997), and 

Confidentiality of Alcohol and Drug Abuse 

Patient Records Regulation and the HIPAA 

Privacy Rule: Implications for Alcohol and 

Substance Abuse Programs (CSAT, 2005). 

Preparing for Implementing Drug 

Testing 

Before starting a drug testing program, it is

recommended that the practitioner discuss

the needs of the program with the laboratory

toxicologist or other knowledgeable laboratory

staff. Some important areas to obtain

information about and to understand include: 

•		The strengths and limitations of the

different tests; 

•		Standard collection procedures; 

•		Possible cross-reactivities with the 

targeted drugs that could affect test

results; 

•		Limitations of the tests offered by the

laboratory; 

• Windows of detection for different 

specimens; 

• Confirmatory testing, which can be done

automatically, or only with specific request

of the practitioner; 

•		Cutoff levels and whether they are

appropriate for clinical purposes; and 

•		Cost of clinical drug test panels. 

When ordering a laboratory test to detect

substances of abuse, practitioners and

staff need to order the correct test for the 

substances of interest and complete the

required forms accurately. The practitioner

needs to know exactly what a test is—and is

not—measuring. For example: 

• The specific drugs or metabolites that can

be detected by the test 

•		The cutoff concentration used by the

laboratory or the point-of-care test (POCT) 

• The specific substance, class of substances,

cross-reacting drugs, and/or metabolites

that may yield a positive test result 

•		The drugs, drug classes, and/or their

metabolites for which the test is being done 

•		The drugs/drug classes that will not be

detected by the test 

Collecting Specimens 

No matter what the reason for drug

testing, collections of specimens have more

similarities than differences. As in workplace

drug testing, which has specific requirements

for collecting samples, clinical drug testing

should have established collection procedures

for that facility or office that follow the

College of American Pathologists, Clinical

Laboratory Improvement Amendments,

and local and State regulations. A properly

collected specimen is essential to a obtaining

an accurate test result, whether for a POCT 

or for a test performed at a laboratory. The

person responsible for specimen collection

needs proper training. His or her duties

include: 

•		Establishing the identity of the patient; 

•		Explaining clearly the collection procedure

to the patient; 

•		Ensuring that the collection container is

appropriate for the specimen matrix; 

•		Labeling the specimen properly; 

• Collecting a sufficient amount of the

specimen; 

•		Ensuring that the specimen collection

method prevents substitution, dilution, or

adulteration; 
Clinical Drug Testing in Primary Care

•		Preventing contamination from

environmental sources when collecting

specimens; 

•		Storing the specimen according to

the manufacturer’s or laboratory’s

recommendations (e.g., proper

temperature) to maintain specimen

integrity;
 

•		Preventing loss of or tampering with

specimen by storing it in a secure area; 

•		Properly recording information; and 

•		Following universal precautions (e.g.,

wearing gloves and a mask, proper

disposal of contaminated materials). 

Collection procedures for drug testing should

be conducted in ways that preserve patients’

dignity. The procedures should be written

and explained to patients before collection.

Product inserts should be the basis for 

written protocols and not used as directions

when actually collecting and testing

specimens or reporting results. 

The results of a drug test will not 

provide a diagnosis of an SUD. 

Conducting POCTs 

Personnel assigned to conduct the POCTs

need to: 

•		Have access to current product inserts for

the laboratory collection device and for the

POCT device, if it is a combined collection 

and testing device; 

•		Pay close attention to the instructions

provided with the test, particularly

regarding timing and reading the results

accurately; 

•		Understand possible cross-reactivities with

other substances, especially if they are

interpreting the results; 

•		Assay appropriate positive and negative

quality control samples; 

•		Decide under what circumstances 

laboratory confirmatory tests will be

ordered; and 

•		Record test results according to the

protocols established by the practice. 

If a practitioner is giving immediate

feedback to a patient—a major benefit of

using POCTs— the practitioner needs to be

confident about what the test is measuring,

its results, and the limitations of the test. 

POCT manufacturers generally have a

technical assistance telephone line to

answer questions. Chapter 5 provides details

about using urine drug tests for specific

drugs, including windows of detection,

cross-reactivities, limitations, and special

considerations for interpreting results. 

Interpreting Drug Test Results 

A drug test indicates whether a substance

or a prescribed medication is present at

levels below (negative) or above (positive)

the test cutoff concentration. A test result 

can reveal that a specimen is negative,

positive, adulterated, substituted, or dilute.

Generally, drug testing cannot tell the

practitioner the amount of drug ingested by

the patient, whether a therapeutic level has

been achieved (e.g., opioids for pain relief),

or frequency of use, nor can it indicate the

patient’s level of intoxication, impairment, or

severity of abuse, when trying to determine

whether a patient may have an SUD. The

results of a drug test will not provide a

diagnosis of an SUD. 

When interpreting drug test results, the

practitioner must know exactly what a test

is—and is not—measuring. The practitioner

must consider: 

•		The purpose of the drug test; 

•		The limitations of the test used; 

•		The drugs or drug metabolites being

detected and those not being detected; 

•		Potential cross-reactivities; and 

•		The limitations of the selected matrix. 

44 
45 

Chapter 4—Drug Testing in Primary Care

Many other factors need to be considered

when interpreting drug test results (e.g.,

specific substance, class of substances,

cross-reacting drugs and/or metabolites that

may yield a positive result). Drug test results

may raise clinical concerns for practitioners,

or provide reassurance about patient

adherence to treatment. Testing may provide

unexpected information, but should never be

the sole basis for diagnosis and treatment

decisionmaking. Test results should be used

to supplement the information obtained

from a comprehensive patient interview, the

physical examination, and consideration of

the patient’s overall health. 

To appropriately respond clinically, it

is important that there be thoughtful

consideration of drug test results, especially

those that seem unusual for a particular

patient or possibly incorrect. Other clinical

findings must also be considered as well as

drug test results. 

Result: Negative Specimen 

A negative test result means that a particular

substance was not detected at or above the 

cutoff concentration in the specimen. A

negative screening test result is rarely

followed by a confirmatory test, but can

be done if requested by the practitioner.

Laboratories perform confirmatory tests

on positive results, either routinely or only

for certain drug/drug class positives (e.g.,

amphetamines, opiates) (White & Black,

2007), depending on the laboratory. It is

imperative that the clinician is familiar with

the laboratory’s practices and procedures for

testing. 

The practitioner’s response to a negative drug

test result is based on the patient’s diagnosis

and reason for testing: 

•		 If the patient is being treated for an SUD,

consistently negative results—along with

improvement in other areas of the person’s

life—may warrant a change in level of

treatment (e.g., decreased frequency 

of visits, decreased testing frequency,

changing from observed to nonobserved

urine collection). 

•		 If the patient is being prescribed

medications with addictive potential (e.g.,

opioids, sedatives), a negative drug test

warrants a reassessment that may lead

to more frequent drug testing and office

visits. 

A negative drug test does not necessarily

mean the patient has not used a particular

substance or taken the prescribed medication.

Negative test results can occur if: 

•		Errors were made in interpretation of the 

test. 

• The patient has induced enzyme levels

from smoking or liver disease and

eliminates the medication more rapidly

than usual (e.g., methadone). 

•		The patient has a shortened

gastrointestinal tract from surgery and

does not absorb the drug sufficiently for

detection. 

•		The patient ran out of medication. 

•		The patient took the medication but not

when expected or during the window of

detection for the ordered test. 

•		The patient was thirsty and drank

sufficient water to dilute the specimen. 

•		The patient may have consumed an

excessive amount of fluids to deliberately

dilute a urine specimen. 

•		The appropriate test for a particular

medication or substance was not 

performed. 

•		The cutoff concentration used in the test 

was set too high, so small amounts of the

drug/drug metabolites were missed. 

•		The parent drug and/or its metabolites

were excreted before specimen collection

(e.g., outside the detection window). 

•		The specimen may have been adulterated

or substituted. 
Clinical Drug Testing in Primary Care

46 

If a negative confirmatory test result is a

surprise based on the patient’s self-report,

collateral report (e.g., from a spouse or

partner, from a parent stating that he or

she has found drugs or drug paraphernalia

in a child’s room), or other evidence, the

practitioner should reconsider the testing

procedures and assessing the patient’s

behavior. The practitioner could contact

the laboratory and discuss the results with

laboratory personnel, especially to see

whether the negative report came from

values that were just below the laboratory’s

cutoff concentration. Repeated urine testing

could be done, or oral fluid could be tested. 

The practitioner could also consider: 

•		Changing or including additional drugs for

which testing is performed based on the

information received. 

•		Adding specimen validity testing or testing

the original negative specimen for validity. 

•		Changing the matrix tested (e.g., test urine

instead of oral fluid for a longer detection

window), if possible (e.g., based on drug

detection period, sensitivity, ease of

adulteration/substitution of the specimen). 

•		Testing repeated serial urines. 

•		Changing the drug-testing methods (i.e.,

change from POCT to laboratory test). 

•		Determining whether the testing occurred

outside of the detectable window for the 

substance. 

A confirmed negative test result for a patient

receiving a prescribed medication, such

as in pain treatment, is of concern. Again,

the practitioner should first check with the

laboratory about the validity of the test:

Was the cutoff concentration low enough to

measure therapeutic levels of the medication?

In this case, retesting may be appropriate.

Was the correct test performed to detect the

prescribed substance (e.g., oxycodone is not

detected in a standard 5-drug panel)? 

If the negative test result is valid for

prescribed scheduled medications, the 

practitioner must decide how to proceed with

the patient who is, at best, not adhering to

his or her prescribed medication regimen

or, at worst, diverting the medication. For

many reasons, a negative test should not

be used to blame the patient for “diversion”

unless there is other credible, incriminating

information (e.g., witnessed attempts to sell

the medication, drug-seeking documentation

from prescription monitoring programs). 

Result: Positive Specimen 

A positive screening test result means that a

particular substance was detected at or above

the administrative cutoff concentration in the 

specimen. Confirmatory tests are frequently

performed for specimens with positive

screening results. If the patient admits drug

use when informed of positive results from a

POCT, a confirmatory test is not needed. 

False-positive results are possible with

screening (initial) tests. If a presumptive

positive is confirmed by a second methodology,

such as gas chromatography/mass spectrometry

(GC/MS) or liquid chromatography/mass

spectrometry/mass spectrometry (LC/MS/

MS), a false positive is highly unlikely if the

test is performed correctly. If a positive result

is surprising and the patient vehemently

denies recent or current use, the practitioner

should order a laboratory confirmatory

test if such a test is not already part of the

laboratory’s testing agreement. 

Interpretation of positive tests can sometimes

be complex, especially if a patient is being

monitored for abstinence following heavy

drug use. With frequent use, significant bodily

accumulation of drugs can occur with the

consequence that drug metabolite(s) may

be excreted for extended periods. This is

especially true for highly lipid soluble drugs,

such as marijuana (tetrahydrocannabinol)

and phencyclidine, but it also applies to other

drugs, such as cocaine and heroin. A patient

who is recently abstinent may continue to test 

positive for days to weeks depending upon

the drug and pattern of use. Distinguishing

this normal pattern of body elimination of 
47 

Chapter 4—Drug Testing in Primary Care

drugs from new drug use can be difficult.

Huestis and Cone (1998) have published

methods for evaluating creatinine-normalized

cannabinoid urine results between two 

specimens collected at least 24 hours apart

to predict new marijuana use. These models

were more recently updated and improved to

take into account the specific times between

two urine collections (Smith, Barnes, &

Huestis, 2009). In a similar vein, Preston,

Silverman, Schuster, and Cone (1997)

developed a model for differentiating new

cocaine use from residual cocaine metabolite 

excretion during abstinence. These criteria

are based on established pharmacokinetics of

benzoylecgonine and include urine creatinine

normalization for control of variations in 

water intake and excretion. 

If the confirmatory test result is positive for

nonprescribed substances, the practitioner

should review the patient’s use of prescribed

medications, OTC products, and herbal

products to determine whether any of these

may be the source of the positive result (e.g.,

poppy seeds causing a positive for codeine or

morphine; high doses of morphine causing a

positive for hydromorphone). The practitioner

may also retest using a different matrix.

However, it is worth noting that changing

matrices makes interpretation difficult. Hair

provides a longer detection window than do

other matrices. If a hair specimen was used

for testing, a patient could test positive for

drug use, even if he or she has not used the

substance for weeks. Segmenting a hair

specimen is useful to narrow the window in

which a positive is observed. However, hair

testing is expensive. A urine or oral fluid

drug test could provide a more accurate

picture of very recent use. However, if the

second specimen using the same or a different 

matrix is negative, it does not refute the

scientific validity of the first test. 

Clearly, drug test results should never be the

sole criteria used for diagnosis of an SUD or

making treatment decisions. The practitioner

should not take action based solely on drug

test results, but should consider them along

with behavioral and physical assessments 

and any collateral information obtained (with

permission of the patient) from a spouse,

partner, or family member. 

Other possible changes in drug-testing

procedures include: 

•		 Increasing the testing frequency to

discourage illicit drug use by the patient,

or possible diversion of prescribed

medications; 

•		Changing the drugs tested for (e.g., test for

another class of drugs) to detect the full

scope of the patient’s drug use; and 

•		Changing the drug-testing methods (e.g.,

use a laboratory test instead of a POCT or

request a confirmatory test for all initial

tests) to rule out false-positive results. 

Other changes to treatment are discussed

in the section on monitoring patients in

Chapter 4. 

Result: Adulterated or Substituted 

Specimen 

Urine is the easiest specimen to adulterate,

and commercial formulas of synthetic urine

are available for substitution. Other fluids, 

including water, also have been used for

substitution. If the test result indicates 

that the specimen has been adulterated

or substituted, the practitioner collects

another specimen and reviews procedures to

determine whether the temperature and pH

of specimens are being checked immediately

after collection. For patients who seem to

have several test results of adulterated 

or substituted urine, stricter collection 

procedures could be instituted for that

patient. These could include: 

•		Ensuring that adulterants, such as

soap, ammonia, or bleach are not readily

available in the collection area when that 

patient provides specimens; 

•		Prohibiting personal belongings in the

bathroom; 
Clinical Drug Testing in Primary Care

48 

•		Turning off the source of running water

during collection and putting blue dye in

the toilet; and 

•		Observing specimen collection. 

The practitioner should review the patient’s

history, interview the patient, and observe

the patient’s behavior during the interview.

The patient may need to be referred to a

more intensive level of care. The drug-testing

program can also be modified by adding

a specimen validity test to the POCT or

laboratory test, and changing the specimen

matrix (e.g., oral fluid is least likely to be

adulterated). 

Result: Dilute Specimen 

A dilute urine specimen can be negative

or positive, depending upon the degree of

dilution and amount of drug excreted. If the

test result shows that the specimen has been

diluted, the practitioner should discuss both

the dilution and the negative or positive

test result with the patient. In addition, the

practitioner could: 

•		Test a different matrix, if possible; 

•		Collect and test a new specimen; 

•		Review the specimen collection site and

ensure that bluing has been added to the

toilet, that the water is turned off to the 

taps, and that patients are not allowed to

take personal effects into the bathroom; or 

•		Consider medical reasons for diluted 

urine (e.g., conditions, such as routinely

receiving diuretics, resulting in polyuria). 

Result: Invalid Urine Specimen 

An invalid result is one in which scientifically

supportable analytical test results cannot

be established for a specimen. An invalid

laboratory test result for urine can be caused

by many factors, such as: 

•		A physiological inconsistency between

the patient’s urine creatinine and specific

gravity; 

•		An interference in the screening or initial

test analysis; 

• An interference in the confirmatory assay; 

• The presence of oxidizing compounds at or

above a cutoff set by the laboratory; 

•		A urine pH greater than or equal to 3.0 but

less than 4.5 or outside other range set by

the laboratory or POCT manufacturer; 

•		A urine pH greater than or equal to

9.0, but less than 11.0 or outside other 

range set by the laboratory or POCT

manufacturer; 

•		The presence of nitrites in urine at or

greater than 200 μg/mL but less than

500 μg/mL, or above a level set by the

laboratory or POCT manufacturer; 

•		The possible presence of chromium (VI); 

•		The possible presence of a halogen (e.g.,

bleach, iodine, fluoride); 

•		The possible presence of surfactant (e.g.,

soap); 

•		The physical appearance of a specimen

is such that the laboratory feels analysis

of the specimen might damage its

instruments; and 

•		Other factors determined by the laboratory

for an invalid specimen. 

An invalid test result is not definitive proof

of specimen tampering. The practitioner

should consider other possible causes before

assuming that the patient has attempted to

subvert the test. The practitioner could try to

determine the reason for the report or discuss

possible causes with the laboratory (e.g.,

Was an unidentified adulterant suspected?

Were the specimen’s physical characteristics

inconsistent with human urine?). A review

of the patient’s history may reveal a medical

explanation (e.g., a medication that could

have interfered with the test). 

The practitioner could also have another

specimen collected and tested and ensure

that the collector follows proper procedures,

including restricting patient access to 
49 

Chapter 4—Drug Testing in Primary Care

materials that could be used to adulterate or 

substitute the specimen. 

Results are also reported as indeterminate or

inconclusive. The practitioner should consider

the possible causes, including storage and

transport irregularities, and potential

medical explanations (e.g., a medication

that could have interfered with the test).

If this happens often, the practitioner may

want to ask the patient to return for further

discussion and repeat the test. 

Frequency of Testing 

Drug testing can be done when conducting an

assessment when an SUD is suspected, or as

a baseline when prescribing medications with

addictive potential. The subsequent frequency

of drug testing depends on the practitioner,

the individual patient, the diagnosis, and the

reason for drug testing. 

In opioid pain management, testing can

be done both to ensure compliance with

prescribed medications and to identify abuse

of illicit substances. Drugs of interest in

this instance include benzodiazepines and

opioids (e.g., oxycodone, methadone, fentanyl,

hydrocodone, hydromorphone, morphine).

Drug tests can be done before providing

initial prescriptions or refills (White &

Black, 2007) or for other medications with

addictive potential. Testing can also be done

if the patient exhibits aberrant behavior,

if diversion of prescribed medications is

suspected, or randomly to monitor treatment. 

For the patient being treated for an SUD,

drug tests can be done: 

• With changing frequency as the patient

progresses (less often as the patient

progresses, or more often with lack of

progress);
 

•		 If relapse is suspected; 

•		 If the patient exhibits aberrant behavior; 

or 

•		Randomly to monitor treatment. 

For the patients receiving medications,

particularly opioids, with abuse potential,

drug tests can be done during every visit,

randomly, before providing prescription

refills, or if the patient exhibits aberrant

behavior. The frequency can also change with

several drug tests that show that the patient

is taking the medication as prescribed and is

not positive for illicit drugs. 

A drug test may not be needed if the

patient admits illicit drug use or treatment

noncompliance for prescribed medications

when coming to his or her appointment. 

Documentation and 

Reimbursement 

Proper documentation is needed for both patient

record keeping and to obtain reimbursement. 

Documentation 

In addition to keeping accurate patient

medical records, practitioners must ensure

proper documentation of the use of POCTs.

This includes (Howerton et al., 2005): 

• Written procedures for performing POCTs; 

•		 Inventory control—lot numbers and

expiration dates for POCTs; 

•		Documentation of staff training and 

reassessment; 

•		Quality assurance test results; 

•		Documentation of problems and problem

resolution; and 

•		Copies of laboratory test orders and

results. 

Patient medical records should document: 

•		The medical necessity for drug testing; 

•		Tests performed and test results; 

•		Changes made to the treatment plan based

on test results; and 

•		Referrals made. 
Clinical Drug Testing in Primary Care

50 

Reimbursement 

Testing for alcohol or drugs is billed by the

specific biological tests conducted according

to the Current Procedural Terminology (CPT)

codebook (American Medical Association, 2006).

Insurance coverage for alcohol or drug testing

varies by carrier. Careful documentation of

the need for testing assists with obtaining

reimbursement. The current issue of the CPT 

codebook should be consulted to obtain proper

reimbursement. 

Some CPT codes that are used for testing

include: 

•		80100: For qualitative screening tests used

to detect the presence of multiple drug

classes. 

•		80101: For qualitative screening tests used

to detect the presence of one drug class. 

•		80102: For each confirmatory test. 

•		82055: Alcohol testing (any method other

than breath). 

•		82075: Alcohol testing (breath). 

Centers for Medicare & Medicaid Services 

uses different codes: 

• G0430-QW: When multiple drug classes

are tested and the testing methodology

does not use the chromatographic method 

• 80100-QW: When testing for multiple drug

classes that do use the chromatographic

method 

•		G0431: Used, per drug class, when

performing a test for a single drug class 

The medical necessity for testing can

be documented by using International

Classification of Diseases codes (i.e., harmful

use or dependence syndrome) from the 

International Statistical Classification of 

Diseases and Related Health Problems, 

Volume 1: 10th Revision (World Health

Organization, 1992). However, the patient

may want to pay for a drug test and not

submit the cost to the health insurance 

company. This should be discussed with the

patient. 
51 

Chapter 5—Urine Drug Testing for Specific 

Substances 

In This Chapter 

• Window of Detection 

• Specimen Collection 

• Adulteration, 

Substitution, and 

Dilution 

• Cross-Reactivity 

• Alcohol 

• Amphetamines 

• Barbiturates 

• Benzodiazepines 

• Cocaine 

• Marijuana/Cannabis 

• Opioids 

• Other Substances of 

Abuse 

Urine is the most rigorously evaluated and most commonly

used matrix for drug testing (Watson et al., 2006). All results

are affected by laboratory test or point-of-care test (POCT)

cutoff concentrations. Therefore, practitioners should always

consult with laboratory staff when ordering laboratory tests

or carefully read POCT package inserts before using the test.

Numerous POCTs are available for urine drug testing. 

Window of Detection 

The window of detection for urine falls in the intermediate 

range, compared with the detection period or window for other

matrices. Many factors influence the window of detection

for a substance. Factors include, but are not limited to, the 

frequency of use (chronic or acute), amount taken, rate at

which the substance is metabolized, cutoff concentration of 

the test, patient’s physical condition and, in many cases, body

fat. Some hepatic, renal, endocrine, and other pathologies

may extend the detection window. 

Drugs are present in urine from within minutes of use to

several days after, depending on the substance; quantity

ingested; the degree to which the bladder was filled with

drug-free urine at the start of drug use; the patient’s hepatic,

cardiac, and renal function; the patient’s state of hydration;

and drug type. Drugs that are smoked or injected are detectable

in urine samples almost immediately. Detection rates for drugs

taken orally are slower, taking up to several hours and

peaking at about 6 hours (Dolan et al., 2004). 

The window-of-detection estimates used in this chapter

are from several sources: Cone (1997), Dasgupta (2008),

Verstraete (2004), Warner (2003), White and Black (2007),

Wolff et al. (1999), and Wong and Tse (2005). 

Many urine drug tests detect the drug metabolite, rather

than the drug itself. As a general rule, drug metabolites

remain in the body for a longer period than does the parent

drug, allowing for a longer detection period. For example,

when the test is for cocaine using urine, the target compound

is usually the metabolite, benzoylecgonine, rather than the

parent cocaine molecule. 
Clinical Drug Testing in Primary Care

52 

It may be difficult to detect illegal substances

in urine specimens of patients who stop use

for several days before providing a specimen.

Most substances of abuse are detectable in 

urine for approximately 2–4 days (Center for

Substance Abuse Treatment [CSAT], 2006b;

Cone, 1997). However, the detection time may

be prolonged when large, frequent doses are

taken over a long period (CSAT, 2006b). For

example, one dose of intranasal cocaine may

be detectable in urine for 3–5 days using

a cutoff of 300 ng/mL after ingestion, but

daily, heavy cocaine use may be detected for

additional days following discontinuation

of use (Verstraete, 2004). Chronic use of

marijuana may be detectable for up to 30

days after use is stopped. 

Specimen Collection 

Urine collection usually is easier than

collecting blood, and samples are available in

sufficient quantities (Warner, 2003). Urine

sample collection is not usually observed in

primary care settings. Clinical drug testing

usually does not warrant direct observation

that may be necessary in forensic or substance

abuse treatment program testing. However,

if it is suspected that a patient is tampering,

diluting, or adulterating urine specimens,

some measures used in forensic or workplace

testing can be used to prevent this, including: 

•		Directly observing specimen provision; 

•		Turning the water off to the taps and

adding a bluing agent to the toilet tank to

avoid sample dilution; 

•		Not providing hand soap in the restroom

where the sample is being done; 

•		Not storing cleaning agents in the

restroom (e.g., ammonia-containing

products, bleach, toilet cleaning products);

and 

•		Not allowing coats, purses, or bags into the

restroom with the patient. 

Patients who exhibit “shy bladder syndrome”

(inability to void) may need to consume

liquids to provide a specimen (e.g., 8 oz. of

water every 30 minutes, but not to exceed a

maximum of 40 oz. over a period of 3 hours,

or until the patient has provided a sufficient

urine specimen). 

Once the specimen is collected and labeled: 

•		The appearance and color of the urine

sample should be documented. 

•		The use of primary collection containers

with a temperature-sensitive strip on

the outside is recommended, rather than 

placing a thermometer or temperature

strip into the urine. 

•		The urine specimen temperature should be

recorded within 4 minutes of collection; the 

temperature should be between 90°F and

100°F. 

Additional clinical testing, such as a routine

urinalysis (e.g., pH and tests to detect

the presence of oxidizing components and

adulterants) can be conducted on an aliquot

separate from that used for urine drug testing

to avoid any argument that a positive was the

result of a foreign object being placed in the

patient’s urine specimen. 

Adulteration, Substitution, and 

Dilution 

Urine tests can be reported as adulterated,

substituted, or dilute. 

Adulteration 

An adulterated urine specimen is one

containing a substance that is not normally

found in urine or that is normally found,

but is in abnormal concentrations. In vitro 

adulterants are foreign substances added to

the urine specimen after voiding. Adulterants

work by interfering with immunoassay and/

or confirmatory assay function, or they

convert the target drug to compounds not 
Chapter 5—Urine Drug Testing for Specific Substances

53 

detected by the test (Jaffee, Trucco, Levy, &

Weiss, 2007). Ordinary household products

(e.g., laundry bleach, toilet bowl cleaner,

hand soap, vinegar, ammonia, eye drops)

have been used for many years to adulterate

urine specimens to obtain a negative drug

test result (Dasgupta, 2007). Household

products that alter the pH of urine to a value

outside the physiologic range can be easily

detected by determining the pH of the sample

(Dasgupta, 2007). Products such as bleach

and other oxidizing agents can be detected

with a general oxidants assay. 

Numerous types of commercial adulterants

are available via the Internet. The following

list is a summary of such products by active

ingredient (Jaffee et al., 2007): 

•		Glutaraldehyde (e.g., “Clean X”) can

interfere with absorbance rates on 

immunoassay tests, masking the presence

of substances such as the marijuana

metabolite, 11-nor-9-carboxy-THC

(THCCOOH), opioids, cocaine metabolites,

morphine, amphetamine, phencyclidine

(PCP), and most other immunoassay

tests. The presence of glutaraldehyde

usually is detected by observing abnormal

immunoassay results; however, other

substances can also cause an abnormal 

immunoassay result. 

•		Sodium or potassium nitrite (e.g., “Klear,”

“Whizzies”) can mask the presence of

marijuana metabolite in immunoassay

tests and the presence of THCCOOH in

confirmatory tests. Abnormal nitrites in

urine can be detected by a specific nitrites

assay or in a general oxidants assay. 

•		Pyridinium chlorochromate (PCC,

commercially known as “Urine Luck”)

is an oxidizing agent that masks the

presence of THCCOOH and, depending

on the pH of the urine, can affect test

results for morphine. Cocaine metabolites,

amphetamine, and PCP are not affected

by PCC (Dasgupta, 2007). Chlorochromate

and other oxidizers, such as dichromate, 

can be detected in urine using a general

oxidants assay. 

•		Peroxide/peroxidase (e.g., “Stealth”) can

oxidize drugs and their metabolites,

making THCCOOH and lysergic acid

diethylamide (LSD) undetectable by

immunoassay tests. The peroxide/

peroxidase combination may be difficult

to detect in urine that is not fresh because 

both hydrogen peroxide and peroxidase

tend to degrade with time. 

The effectiveness of an adulterant depends on

the amount of the adulterant added and, in 

some instances, the concentration of the drug

in the sample. Specimen validity tests can

detect many adulterants in addition to those

described above. 

Substitution 

Synthetic urine products can be submitted

when collection of a urine specimen is not

observed. These products are premixed

liquids with the characteristics of natural

urine (i.e., correct pH, specific gravity, and

creatinine levels). To achieve the temperature

of recently voided urine, synthetic urine

products can be heated in a microwave or

taped next to a heating pad in a pocket.

Sometimes, another person’s urine is

submitted. 

More commonly, water or a saline solution is

substituted for urine. Thus, a urine specimen

is considered substituted when the creatinine 

concentration on both the initial and the 

confirmatory tests is less than 2.0 mg/dL

and the specific gravity is less than or equal

to 1.0010 or greater than or equal to 1.0200

(Substance Abuse and Mental Health Service

Administration [SAMHSA], 2010b). 

Dilute Specimens 

Diluting the urine sample to the point

where the targeted drug is below the cutoff

concentration is another way to obtain a

negative test result. For instance, consuming

water in more-than-normal quantity and

taking diuretics can dilute the urine sample.

Individuals may also add water from the

tap or toilet bowl to dilute specimens if tap 
Clinical Drug Testing in Primary Care

54 

water is available in the restroom and/or

bluing has not been added to the commode

water. Commercial products are available

that promise to “cleanse the urine.” These

products advocate consuming large amounts

of tea or other fluids, increasing urine volume,

thereby diluting drugs in the urine. Reducing

the amount of time between notice that a 

specimen will be collected and the time of

collection reduces the potential for the patient

to consume enough fluids to dilute the urine. 

A laboratory will report a urine specimen

as dilute in conjunction with a positive or

negative drug test when the creatinine

concentration is greater than or equal to

2 mg/dL and less than 20 mg/dL, and the

specific gravity is greater than 1.0010

and less than 1.0030 (SAMHSA, 2010b).

Dilution may raise suspicion of tampering,

but does not necessarily confirm tampering.

Other factors need to be considered, such 

as whether the patient is taking a diuretic,

eating a strict vegetarian diet, or maintaining

a high state of hydration. Other factors

include whether the patient was working

in hot weather conditions and drank large

amounts of fluid or drank fluids immediately

before providing the specimen. 

Cross-Reactivity 

The cross-reactivity of urine immunoassay

tests varies by drug class. For example,

tests for cocaine measuring its principal

metabolite, benzoylecgonine, have low crossreactivity with other substances. However,

tests for amphetamine/methamphetamine

usually are extremely cross-reactive, and

further laboratory testing using a method

different in principle from immunoassay

(i.e., not a second immunoassay) is required

to confirm amphetamine use (Gourlay et

al., 2010). As stated above, cross-reactivity

is many times viewed as a negative aspect

of immunoassay. However, cross-reactivity

does have a positive side. An immunoassay

that is specific for morphine will detect only

morphine and will miss other opiates (e.g.,

hydrocodone) that a patient might be using 

without the treating physician’s knowledge.

Thus, a general opiates screen is preferred

over a specific test when looking for

opiate-type drugs. Lack of cross-reactivity

also may affect testing, such as that

performed for oxycodone, as discussed

under “opioids.” 

Alcohol 

The window of detection for alcohol is 7–12 

hours. The frequency of alcohol use minimally

affects the window of detection; however, 

ingestion of large amounts results in a longer

detection time in body fluids than ingestion

of a small amount of alcohol. The metabolism 

of ethanol may be accelerated in people who

use chronically or binge. Approximately

90–95 percent of alcohol is oxidized in the

liver before elimination in the urine, and 

only 1–2 percent of ingested alcohol is

excreted unchanged in the urine (Moeller,

Lee, & Kissack, 2008). Because of this rapid

metabolization, blood tests or the standard 

hand-held breath devices (breathalyzers)

are often used, and in clinical settings, urine

alcohol tests are used far less frequently than

are blood tests. 

Urine can be analyzed for alcohol through

chemical assays, enzyme immunoassays, or

gas-liquid chromatography (GLC), with the

most accurate reading produced by GLC.

Urine drug tests for alcohol indicate only

recent ingestion; they cannot identify longterm abuse. Furthermore, a urine ethanol 

can show use prior to the collection of the

urine specimen only within a reasonable

timeframe. Alcohol in blood or a blood product

(e.g., serum, plasma) or a breath alcohol is

required to show impairment and the degree

of impairment. 

Biomarkers, such as the gamma-glutamylpeptidase, carbohydrate-deficient transferrin,

aspartate amino transferase (measured in

serum), and erythrocyte mean cell volume

tests may confirm a suspicion of long-term

alcohol abuse or dependence. Ethyl glucuronide

EtG) and ethyl sulfate are direct metabolites 
Chapter 5—Urine Drug Testing for Specific Substances

55 

of ethanol that can be measured in urine. 

Testing for EtG is becoming more common to

monitor alcohol consumption for people who

have been ordered to abstain. However, more 

research is needed to establish standards 

to rule out possible exposure to alcohol in

commercial products, such as mouthwash and

hand sanitizers, versus drinking of alcoholic

beverages (CSAT, 2006a). More information

about biomarkers for alcohol use disorders is 

in The Role of Biomarkers in the Treatment of 

Alcohol Use Disorders, 2012 Revision. 

Amphetamines 

The SAMHSA workplace cutoff concentration

for amphetamines is 500 ng/mL for initial

testing, and 250 ng/mL for confirmatory

testing. To be reported positive for

methamphetamine, a specimen must also

contain amphetamine at a concentration

equal to or greater than 100 ng/mL

(SAMHSA, 2008). 

The window of detection varies. A single dose

of amphetamine or methamphetamine can

be detected in the urine for approximately

24 hours, depending upon urine pH and

individual metabolic differences. People

who use chronically and at high doses may

continue to have positive urine specimens for

2–4 days after last use (SAMHSA, 2010b).

Methylenedioxyamphetamine (MDA),

methylenedioxymethamphetamine (MDMA),

and methylenedioxyethylamphetamine

(MDEA) can be detected for 1–2 days (Moeller

et al., 2008; SAMHSA, 2010b). 

Drug tests for the presence of amphetamine

are among the hardest to interpret.

Methamphetamine is the target analyte for

amphetamine/methamphetamine testing.

Immunoassay tests are highly cross-reactive

and may detect other sympathomimetic

amines, such as pseudoephedrine, readily

available as over-the-counter (OTC)

products. Structural similarities of many

OTC products—including diet agents;

decongestants; and several prescription

medications, such as those to treat attention 

deficit/hyperactivity disorder, narcolepsy,

and Parkinson’s disease, or to suppress

appetite—can cause initial positive test

results. Adderall is an amphetamine and will

result in a positive test for amphetamine. 

Methamphetamine exists as two optical

isomers (stereoisomers) that are designated 

d- and l-. The d-form has high abuse

potential. The l-form in therapeutic doses

has a primarily peripheral action and is

found in some OTC products (Kwong, 2008a,

2008b). Immunoassay tests for amphetamine

and methamphetamine can be divided

into two types: (1) those designed to detect

amphetamine and methamphetamine, only;

and (2) those that also have variable

cross-reactivities with “designer

amphetamines,” such as MDA, MDMA, and

MDEA, as well as with sympathomimetic

amines (e.g., ephedrine, phentermine,

pseudoephedrine, phenylpropanolamine)

(Kwong, 2008a, 2008b). 

Typical immunoassay tests do not distinguish

methamphetamine and/or amphetamine

use from use of OTC products containing

sympathomimetic amines. All presumptively

positive urine “amphetamines” results should

be confirmed by an alternate methodology

different in principle from the immunoassay

used to produce the screening result (White

& Black, 2007). A confirmed test by gas

chromatography/mass spectrometry (GC/MS)

for methamphetamine can either be 

d-methamphetamine (licit or illicit) or

OTC nasal spray. A confirmed test for

methamphetamine is insufficient to

distinguish illicit drug use from use of an

OTC product. A separate test is available

that is offered by most laboratories that

distinguishes illicit methamphetamine

(d-methamphetamine) from OTC nasal

inhaler (l-methamphetamine). This

specialized confirmatory test, stereospecific

chromatography, is necessary to distinguish

methamphetamine, amphetamine, and their

isomers from legitimate sympathomimetic

agents (Gourlay et al., 2010). However, a

result confirmed by a second methodology,

such as GC/MS, is definitively amphetamine 
Clinical Drug Testing in Primary Care

56 

and/or methamphetamine. Cross-reactivity

with MDMA, MDA, and/or MDEA is beneficial

in that, once confirmed by an alternate

methodology, it may uncover a previously

unsuspected substance abuse problem. 

Patients should be advised to avoid the use 

of this type of OTC nasal spray when being

tested. A confirmed test for amphetamines

or methamphetamines can occur because a

number of other prescription medications

metabolize to these isomers. The patient

needs to be questioned regarding the reasons

for taking the medication to determine

whether it is by prescription or is being

misused. 

Tests for amphetamine cross-react with

several other substances and are too 

numerous to present a comprehensive

list. A confirmed test for amphetamine or

methamphetamine can occur because a

number of other medications metabolize 

to these. The product inserts should be

consulted for the current list of cross-reacting

drugs. Substances known to metabolize to

methamphetamine and amphetamine include

benzphetamine, dimethylamphetamine,

famprofazone, fencamine, furfenorex, and

selegiline (SAMHSA, 2010b). Substances

known to metabolize to amphetamine

include amphetaminil, clobenzorex,

ethylamphetamine, fenethylline, fenproporex,

mefenorex, mesocarb, and prenylamine

(SAMHSA, 2010b). 

Barbiturates 

The incidence of barbiturate abuse is low 

compared with abuse of other drugs or

alcohol (SAMHSA, 2009). Barbiturates (sans 

phenobarbital) are detected easily using a

variety of immunoassays, even though only

a small amount of the parent drug is found

in the urine. The use of barbiturates may

be confirmed readily using several different

methods including, but is not limited

to, GC/MS and liquid chromatography/

tandem mass spectrometry (LC/MS/MS)

due primarily to the high doses commonly

administered or taken (Levine, 2010). Most

urine immunoassay tests use secobarbital as

the calibrator, at a cutoff concentration of 200 

ng/mL or 300 ng/mL. Cross-reactivity with

other barbiturates varies with this assay,

and the detection window is dose dependent.

Several commonly used assays generally

cross-react with and detect butabarbital and 

amobarbital (Kwong, 2008b). The window of

detection depends on the type of barbiturate

(see Exhibit 5-1). 

Exhibit 5-1. Barbiturates—Window of Detection 

Selected Barbiturates Window of Detection 

Short acting (e.g., pentobarbital, secobarbital) 4–6 days after the last use (cutoff of 300 ng/ml) 

Intermediate acting (e.g., amobarbital, butabarbital) 3–8 days (cutoff of 300 ng/mL) 

Long acting (e.g., phenobarbital) 10–30 days (cutoff of 300 ng/mL) 

Sources: Baselt (2008); White & Black (2007). 

Benzodiazepines 

The results of urine drug tests for

benzodiazepines may be challenging to

interpret without a basic knowledge of

the pharmacokinetics of the different

benzodiazepines. Like barbiturates,

benzodiazepines are classified by their

elimination half-lives. It is important to

know a test’s sensitivity and specificity

for the benzodiazepine in question.

False-negative results can occur if a test

is set to detect only one benzodiazepine or

its primary metabolite(s), and the clinician

is trying to monitor a non-cross-reacting

benzodiazepine. Because the parent drug

in the benzodiazepine class is usually

undetectable in urine drug tests,

drug-screening immunoassay tests are

usually designed to detect a specific metabolite, 
57

Chapter 5—Urine Drug Testing for Specific Substances

57 

either unconjugated oxazepam or its

glucuronide conjugates. Immunoassay tests

are more likely to detect benzodiazepines that

are metabolized to the targeted compound

and may miss the other non-cross-reacting

compounds. 

Benzodiazepines can be divided into several

groups, based on their metabolites: 

• Some benzodiazepines (e.g.,

chlordiazepoxide, diazepam, temazepam)

are metabolized to oxazepam. Oxazepam

is conjugated into an inactive glucuronide

metabolite. 

• Nitrobenzodiazepines (e.g., clonazepam

which is primarily reduced to

7-aminoclonazepam, which is further

metabolized) are usually reduced to the

corresponding amino compound, but

are not converted into oxazepam or its

conjugate. 

• The triazolobenzodiazepines such

alorazepam, estazolam, and triazolam

tend to form hydroxyl derivatives that are

separate and distinct from oxazepam. 

• Other benzodiazepines (e.g., lorazepam,

flurazepam) have a unique metabolism

that does not result in the formation of 

oxazepam. 

Clinical laboratories usually use cutoff

concentrations of 200 ng/mL or 300 ng/mL,

which can detect use of a benzodiazepine, but

may not necessarily detect a low therapeutic

dose (e.g., triazolam) (Warner, 2003). 

Flunitrazepam (Rohypnol), commonly known

as “Roofies,” is a Schedule I substance. 

Flunitrazepam is one of the so-called “daterape” drugs and shows good to excellent

cross-reactivity in most commercial urine

benzodiazepine assays except the Neogen,

Immunalysis, and Randox assays. If ingested,

flunitrazepam and/or its metabolites may

be detected for approximately 4–12.5 days

at higher doses (White & Black, 2007).

See Exhibit 5-2 for estimated windows of 

detection of some of the most commonly

prescribed benzodiazepines. 

Exhibit 5-2. Benzodiazepines—Window of Detection* 

Benzodiazepines Estimated Window of Detection 

Short acting (e.g., triazolam) Up to 24 hours 

Intermediate acting (e.g., alprazolam, clonazepam, 

lorazepam, temazepam) 

1–12.5 days 

Long acting (diazepam) 5–8 days for diazepam 

6–24 days for the active metabolite, nordiazepam 

Chronic abuse of benzodiazepines Up to 30 days after the last dose 

*Higher doses and some pathologies may extend the window of detection. 

Source: White & Black (2007). 

Cocaine 

The Federal workplace cutoff concentration

for initial testing for cocaine is 150 ng/

mL, and confirmatory testing for cocaine

metabolite (benzoylecgonine) is 100 ng/mL

(SAMHSA, 2008). 

Urine drug tests for cocaine detect cocaine’s

major metabolite, benzoylecgonine. The body

quickly metabolizes cocaine to its major

metabolite, benzoylecgonine, and neither

is stored in the body. Therefore, even with

chronic use, the window of detection is 1–3 

days (Jufer, Walsh, Cone, & Sampson-Cone,

2006), with the clinical test cutoff of

300 ng/mL. The detection window may be

longer using the federally mandated cutoffs. 

Urine immunoassay tests for cocaine are

highly specific and detect use of powder

(snorting or insufflation), parenteral use, oral

ingestion, smoked, or use of crack cocaine.

Among the possibilities of products they 
Clinical Drug Testing in Primary Care

58 

 

cannot distinguish is “Inca” tea or “coca”

tea—made from coca leaves—because they

contain cocaine. Ingestion of tea prepared

from coca leaves produces positive urine tests

for benzoylecgonine (Jenkins, Llosa, Montoya,

& Cone, 1996). 

Immunoassay tests are highly specific for the

cocaine metabolite (benzoylecgonine) and do

not cross-react with other substances. 

Marijuana/Cannabis 

The SAMHSA workplace cutoff concentration

for cannabinoid metabolites is 50 ng/mL

for initial testing. The confirmatory testing

cutoff for cannabinoid metabolite (delta-9­

tetrahydrocannabinol-9-carboxylic acid) is 15

ng/mL. 

Marijuana, the most commonly used illicit

drug, can be detected for prolonged periods

after regular use. The active principle of

marijuana, tetrahydrocannabinol (or THC)

has high lipid solubility. The THC that is

stored in fatty tissue gradually reenters the

bloodstream at very low levels, permitting

metabolism and eventual excretion. THC is 

metabolized extensively in the liver. 

The window of detection is highly dependent

on the quality of the marijuana, the

individual’s body fat content and metabolism,

chronicity of use, the individual’s state of

hydration when the urine sample is collected,

and the cutoff used by the laboratory (White

& Black, 2007). Approximate window of

detection times are as follows: 

• Up to 3 days for single use 

• Up to 4 days for moderate use 

• Up to 10 days for heavy use 

• 30–36 days for chronic, heavy use 

Marijuana is easily detected by immunoassay.

Generally, laboratory tests for marijuana use

are designed to detect THC-COOH (11-norΔ9-tetrahydrocannabinol-9-carboxylic acid;

commonly referenced as THC acid or THCA), 

the major inactive metabolite of THC.

Laboratory tests are available with cutoff

concentrations of 20 ng/mL, 50 ng/mL, or

100 ng/mL, although the majority of

laboratories employ 50 ng/mL. The 20 ng/mL

cutoff is commonly used clinically (White &

Black, 2007). The 100 ng/mL cutoff is rarely

used due to its lack of sensitivity. 

Confirmation by GC/MS tests should

be performed if the positive screening

test results have legal or other serious

implications for the patient. Some legal

food products are made from hemp seeds

(e.g., hemp seed oil, flour, liquor, ale). These

products do not appear to be psychoactive,

but, after a person has ingested these food

products, THC metabolites have been

detected in urine specimens. However,

usually the THC concentrations in the food

products are too low to produce a positive

urine drug test result (Bosy & Cole, 2000).

Some proton-pump inhibitors have caused

positive tests on immunoassay (Gourlay et

al., 2010). 

The literature is mixed on the test results 

of passive exposure to marijuana. Under

extreme conditions (e.g., the person rides in

a closed car with people smoking marijuana),

passive exposure can lead to positive results

with a screening cutoff of 20 ng/mL. However,

the levels of marijuana metabolites found

in urine under less extreme passive

exposure conditions are below the 50 ng/mL

(employment-related) cutoff concentrations

and would not be detected (Cone et al., 1987;

Perez-Reyes, Di Guiseppi, & Davis, 1983).

Marinol and Sativex cause positive results

because they contain THC. 

Opioids 

Clinical urine opioid drug testing is done to

detect illicit opioid use, monitor adherence

to pain treatment with opioids (especially

in pain management clinics), and monitor

adherence to methadone treatment. 

Practitioners need to be particularly careful

when interpreting urine drug test results 
59

Chapter 5—Urine Drug Testing for Specific Substances

59 

for opioids. It is essential to understand the

metabolism of this class of drugs to interpret

drug tests. 

The term opioids includes both opiates and

opioids. Opioids are a group of compounds

that have pharmacological properties

similar to morphine and have affinity

toward the opiate receptors in the brain

(Dasgupta, 2008). The term opiates refers 

to naturally occurring alkaloids (morphine

and codeine) obtained from the opium

poppy and semisynthetic alkaloids that are

partially derived from the opium poppy (i.e.,

buprenorphine, dihydrocodeine, heroin,

hydrocodone, hydromorphone, levorphanol,

oxycodone, and oxymorphone) (Dasgupta,

2008). Opioids include the synthetic

compounds that are structurally unrelated

to morphine (i.e., fentanyl, meperidine,

methadone, pentazocine, propoxyphene,

tramadol) (Dasgupta, 2008). 

Opiate immunoassay tests were originally

designed to detect morphine and codeine as

target analytes to identify heroin use (Kwong,

2008a, 2008b). Morphine is a metabolite of

heroin (Warner, 2003). Many laboratories

use SAMHSA’s Federal workplace cutoff

concentrations for opiates and test for

morphine, codeine, and 6-acetylmorphone

(6-AM). However, for opiates, a cutoff

of 300 ng/mL is commonly preferred 

clinically (White & Black, 2007). As heroin

is metabolized, 6-AM is produced, which

is then hydrolyzed to morphine. Thus, the

detection of 6-AM in the urine proves heroin

use, but 6-AM is eliminated quickly from

the body, making detection in urine possible

for only a few hours (Gourlay et al., 2010).

A typical opiate screen reports the presence

of only codeine and morphine. An expanded

opiate panel may also include hydrocodone

and hydromorphone and/or oxycodone and

oxymorphone (see Exhibit 5-3). 

Exhibit 5-3. Opioids—Window of Detection* 

Opioid Window of Detection Cutoffs 

Buprenorphine Up to 4 days 0.5 ng/mL 

Codeine 1–2 days 300 ng/mL 

Heroin metabolite (6-acetylmorphine [6-AM]) 1–3 days 10 ng/mL 

Hydrocodone 1–2 days 100 ng/mL 

Hydromorphone 1–2 days 300 ng/mL 

Methadone (maintenance dose) 3–11 days 300 ng/mL 

Morphine 1–2 days 300 ng/mL 

Oxycodone (immediate-release formulation) 1–1.5 days 100 ng/mL 

Oxycodone (controlled-release formulation) 1.5–3 days 100 ng/mL 

Oxymorphone (immediate-release formulation) 1.5–2.5 days 100 ng/mL 

Oxymorphone (extended-release formulation) 1–4 days 100 ng/mL 

*Higher doses and some pathologies may extend the window of detection. 

Sources: Kronstrand et al. (2008); White & Black (2007). 

Distinguishing between illicit opioid use

and the use of prescribed opioid medications

can be difficult. Immunoassay tests have

variable cross-reactivity with semisynthetic

opioids (i.e., hydrocodone, hydromorphone)

and may or may not detect their use.

The synthetic opioids (e.g., meperidine,

fentanyl, methadone) are structurally

dissimilar enough from morphine that they

are not detected in standard opioid urine

immunoassay tests, although some

cross-reactivity—especially with the

metabolites—may exist. Separate

immunoassay tests specifically designed

for their detection must be used. Oxycodone

and its active metabolite, oxymorphone,

require a drug-specific test. Specific assays

for oxycodone are available as both POCTs

and laboratory tests. Specialized tests for

synthetic opioids must be ordered when 
Clinical Drug Testing in Primary Care

60 

concerns exist about abuse or diversion 

of synthetic opioid pain medications or to

monitor patients’ use of buprenorphine or

methadone. Many laboratories have specific

pain medication panels that test for codeine,

morphine, hydrocodone, hydromorphone,

oxycodone, fentanyl, and buprenorphine

(Gourlay et al., 2010). Buprenorphine has

potential for abuse, especially in the standalone preparation—Subutex (Smith, Bailey,

Woody, & Kleber, 2007). 

Poppy seeds can contain morphine and

codeine. Ingesting large amounts of poppy

seed or products containing poppy seeds

can cause a positive urine drug test result.

The urine drug test result will show that

morphine and, possibly, codeine are present,

and the practitioner needs to determine

whether poppy seeds are the source. The

original employment-related and clinical

cutoff concentration for morphine and codeine

was 300 ng/mL, but was increased to

2,000 ng/mL to avoid positive test from poppy

seed consumption (often cited as the “poppy

seed defense”). This higher cutoff minimized

opioid-positive test results from poppy seeds,

but also reduced the likelihood that opioid

use would be detected. 

Methadone is a synthetic opioid used for

treatment of opioid dependence and chronic

pain and is not detected in standard opioid

drug tests. Specific tests for methadone and

its major metabolite EDDP (or 2-ethylidene1,5-dimethyl-3,3-diphenylpyrrolidine)

exist and are used to monitor adherence 

to medication-assisted treatment and to 

check for illicit drug use. These methadone

immunoassay tests have little cross-reactivity

with other opioids. Therefore, a positive

opioid drug test result for a patient on

methadone suggests the use of other opioids.

The cutoff concentration is generally set at

300 ng/mL and can detect methadone in urine 

for several days after the last therapeutic dose.

To confirm that the patient has taken

methadone and is not simply adding it to a

urine specimen, the test for the methadone

metabolite, EDDP, can be ordered. If a 

practitioner is caring for a patient on 

methadone maintenance treatment for opioid

dependence, the practitioner can ask the

patient to sign a release of information to

obtain the patient’s urine test results from

the opioid treatment program. 

Other Substances of Abuse 

Testing information for other substances is

presented below. 

PCP 

The SAMHSA revised workplace cutoff

concentration for PCP is 25 ng/mL for initial

testing. The confirmatory testing cutoff for

PCP is 25 ng/mL. This cutoff is often used

for clinical purposes, as well. Federally

regulated laboratories are required to test

for PCP; other laboratories are not. Directors 

of clinical laboratories may add PCP to their

screening drug panel if PCP use is prevalent

in the community. The window of detection

for PCP from casual use is 1.5–10 days

(urine pH-dependent) and for up to several

weeks with chronic use. The metabolite of 

dextromethorphan can cross-react with PCP

and could cause a false positive. 

When used to adulterate urine specimens,

table salt, sodium hypochlorite, sodium

hydroxide, detergent, and soap cause falsenegative test results (Jaffee et al., 2007).

However, these adulterants can be detected 

if the pH and specific gravity of the urine

samples are checked. 

Club Drugs 

Club drugs generally include

gamma-hydroxybutyrate (GHB), ketamine,

flunitrazepam (Rohypnol, or “Roofies”),

MDMA, MDA, and MDEA. Urine drug

screening tests do not generally screen for

club drugs. However, please see the section

above on amphetamines for information

about MDMA, MDA, and MDEA, and the 

section on benzodiazepines for information on

flunitrazepam (Rohypnol, or “Roofies”). New

drug tests may screen for some club drugs, 
Chapter 5—Urine Drug Testing for Specific Substances

but routine drug tests cannot detect ketamine

or GHB. Testing for GHB can be done by using

GC or high-performance LC (LeBeau et al.,

2006). The window of detection for GHB is

generally less than 12 hours. Two commercial

enzyme-linked immunosorbent assays

(ELISAs) that test for ketamine are available

(Huang et al., 2007). For a single dose of

ketamine, detection is possible for about 3

days at a cutoff of 50 ng/mL (Baselt, 2004;

Cone & Huestis, 2007). 

LSD 

Very little of the parent drug, LSD, is

excreted in urine and it can be detected 

for only approximately 4 hours. The

most abundant metabolite is nor-LSD 

(N-desmethyl-LSD), which is generally

detected at a cutoff level of 0.5 ng/mL.

Confirmatory testing is usually done with

LC/MS or LC/MS/MS. 

Inhalants 

No standard drug test can detect inhalant

use. Most inhalants contain many compounds,

and no single assay can test for all of them.

Some laboratories can test for inhalants 

using specially ordered tests, primarily with

GC. Collection of a specimen for inhalants

requires that the specimen be appropriately

and rapidly sealed to ensure that the volatile

inhalants are not lost. 

Toluene is the main substance in many

inhalants. It is cleared from the body quickly,

leaving a short period to detect exposure.

Most laboratories are unable to test for this 

substance. Urinary hippuric acid (UHA)

measurements can be adapted to detect

toluene inhalation, but they should be used

cautiously because a person’s metabolism can

raise the levels of UHA. Thiesen, Noto, and 

Barros (2007) report that UHA levels higher

than 3.0 g/g creatinine indicate intentional 

exposure. 

61 

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Appendix B—Laboratory Initial 

Drug-Testing Methods 

Testing Method Description Advantages Disadvantages/ 

Cautions 

Cloned Enzyme Donor 

Immunoassay (CEDIA) 

•	An immunoassay using enzyme 

(ß-glucuronidase) fragments 

engineered by recombinant DNA 

techniques. 

•	Two fragments, the enzyme donor 

and enzyme acceptor, are inactive 

when separated. 

•	Based on competition for antibody 

binding sites between drug 

conjugated with enzyme donor (ED) 

and drug in the specimen. 

•	Enzyme activity decreases when the 

ED drug fragment is bound, so the 

drug concentration in the specimen 

can be measured by an increase of 

enzyme activity. 

•	 Same reliability 

as EMIT in 

screening for 

barbiturate use. 

•	May produce 

false-positive results 

for amphetamines 

and lysergic acid 

diethylamide when 

bupropion is used. 

Enzyme-Multiplied 

Immunoassay 

Technique (EMIT) 

•	An immunoassay based on 

competition for antibody binding 

sites between drug in the specimen 

and drug labeled with an enzyme. 

•	Enzyme activity decreases on 

binding to the antibody, so the 

drug when present in the specimen 

can be measured by an increase in 

terms of enzyme activity. 

•	Widely used. 

•	 Simple to 

conduct (same 

as CEDIA or 

KIMS). 

•	Poor performance 

record (high rate 

of false-positive 

results in some 

studies). Many 

over-the-counter 

(OTC) preparations 

can cause falsepositive results for 

amphetamines and 

phencyclidine (PCP) 

assays. 

Enzyme-Linked 

Immunosorbent Assay 

(ELISA) 

•	A competitive binding enzyme 

immunoassay using drug-specific 

antibodies immobilized on the sides 

of a microplate well. 

•	The most 

versatile and 

commonly used 

immunoassay. 

•	Customized 

tests developed 

for different 

settings, 

substances, 

purposes, and 

matrices. 

•	 Labor intensive. 

•	Poorly suited for 

automation. 

71 
Clinical Drug Testing in Primary Care

Testing Method Description Advantages Disadvantages/ 

Cautions 

Fluorescence 

Polarization 

Immunoassay (FPIA) 

•	An immunoassay based on 

competition between the drug in 

the specimen and drug labeled with 

a fluorophore. 

•	 Light emitted by the fluorescently 

labeled drug/antibody complex is 

more polarized. 

•	The specimen’s fluorescence 

polarization value is inversely related 

to the drug concentration. 

•	 Sensitive. 

•	 Specific. 

•	Cannot be 

automated 

conveniently. 

Kinetic Interaction of 

Micro-particulates in 

Solution (KIMS) 

•	An immunoassay based on the 

principle of the kinetic interaction 

of microparticles in a solution 

where the drug content of the 

urine is directly proportional to 

the inhibition of the microparticle 

aggregation. 

•	May be used 

to test a wide 

variety of drugs 

of abuse. 

•	Cross-reacts 

with some OTC 

preparations 

when testing for 

amphetamines. 

Sources: Armbruster, Hubster, Kaufman, & Ramon (1995); Center for Substance Abuse Treatment (2006b); Neerman (2006); Verebey, 

Meenan, & Buchan (2005); Vidal & Skripuletz (2007). 

72 
Appendix C—Laboratory Confirmatory 

Drug-Testing Methods 

Testing Method Description 

Gas Chromatography (GC) •	A technique for separating and analyzing compounds that can be 

vaporized without chemicals. 

High-Performance Liquid 

Chromatography (LC) 

•	A chromatographic technique for separating and analyzing chemical 

substances in solution. 

•	 Separation is based on absorption, partition, ion exchange, and/or size 

exclusion. 

GC/Mass Spectrometry 

(GC/MS) 

•	A combined technique coupling an MS (mass spectrometer or mass 

selective detector) with a GC instrument. 

•	After the GC has separated the analytes in a specimen, the components 

enter the MS, which identifies and quantifies the separated analytes. 

•	The MS creates charged particles (ions) and separates them according to 

their mass-to-charge ratio. 

•	The ions form unique mass spectra, which are used to identify analytes. 

•	Most common method of confirmation. 

GC With Tandem 

MS (GC/MS/MS) 

•	The same principles, as described above. 

•	The MS produces and isolates the ion of interest, which is then reacted 

with a reagent gas to produce fragments. 

•	The MS scans the fragments (called the “productions”) to obtain 

structural information. 

•	This method is more sensitive than GC/MS. 

LC With MS (LC/MS) •	 LC can accommodate nonvolatile compounds. 

•	 Separation is based on distribution of the solutes between a liquid mobile 

phase and a stationary phase. 

•	MS phase is the same as described above. 

•	Widely used for pain management. 

LC With Tandem MS 

(LC/MS/MS) 

•	Described above, with two MS phases. 

•	Also used in pain management. 

73 

Appendix D—Laboratory Specimen 

Validity-Testing Methods 

Testing Method Analytes Description 

Colorimetry Specific gravity, 

pH, creatinine, 

adulterants (general 

or specific tests) 

•	A technique that compares the color developed in 

a solution of a test material with that in a standard 

solution, quantitated on the basis of the absorption of 

light. 

•	The concentration of the analyte is determined by 

visually noting the color or electronically measuring 

the intensity of light at selected wavelengths (i.e., 

spectrophotometry). 

Refractometry Urine-specific gravity •	A method for determining the amount of solute (i.e., 

urinary total solids) in the urine by measuring the index of 

refraction. 

•	A urine specific gravity refractometer displays specific 

gravity values converted from refractive indices. 

Potentiometry pH •	An instrument (e.g., pH meter) that measures hydronium 

ion activity and converts it into the negative logarithm 

(base 10), which is the displayed pH. 

Atomic Absorption 

Spectrophotometry 

Adulterants •	A method in which the specimen atoms in the vapor 

phase absorb ultraviolet or visible light and transition to 

higher electronic energy levels. 

•	The analyte concentration is determined from the 

amount of absorption of specific wavelengths. 

Capillary 

Electrophoresis (CE) 

Adulterants •	A technique based on the mobility of ions in an electric 

field. 

•	Positively charged ions migrate toward a negative 

electrode, and negatively charged ions migrate toward a 

positive electrode. 

•	 Ions have different migration rates depending on their 

total charge, size, and shape and can therefore be 

separated. 

•	CE is an electrophoretic method using a small-bore, 

fused silica capillary tube. 

Gas Chromatography/ 

Mass Spectrometry 

(GC/MS) 

Adulterants •	 Full-scan MS or selected ion monitoring identifies 

unknown analytes. 

•	The identification of the analyte of interest relies on 

a comparison with the mass spectra of an analyzed 

reference standard or reference library spectra. 

Inductively Coupled 

Plasma/MS 

Adulterants •	A combined analytical method in which a vaporized 

sample is introduced into a radio frequency-induced 

plasma, is ionized, and then enters an MS for 

identification and quantification. 

75 
Clinical Drug Testing in Primary Care

76 

Testing Method Analytes Description 

Multi-Wavelength 

Spectrometry 

Adulterants •	A method that uses multiple wavelengths of light (or 

other electronic transmissions) to identify an analyte. 

•	The method generates corrected absorbance values that 

are related to the analyte concentration. 

Ion Chromatography Adulterants •	A form of liquid chromatography that uses ion-exchange 

resins to separate atomic or molecular ions based on 

their interaction with the resin. 
77 

Appendix E—Glossary
 

adulterated specimen. A specimen containing either a substance that is not a normal

constituent for that type of specimen or containing an endogenous substance at a concentration

that is not a normal physiological concentration. 

adulteration panel. Testing a specimen for substances that mask the presence of illegal drugs

in that specimen. 

aliquot. A fractional part of a specimen. 

analyte. Any material or substance subjected to analysis (testing). 

chain of custody. Procedures to account for the integrity of each specimen or aliquot by tracking

its handling and storage from point of specimen collection to final disposition of the specimen

and its aliquots. 

concentration. Amount of a drug in a unit volume of biological fluid expressed as

weight/volume. Urine concentrations are usually expressed as nanograms per milliliter (ng/

mL), micrograms per milliliter (ug/mL), or milligrams per liter (mg/L). 

confirmatory drug test. A second analytical procedure performed on a different aliquot of the

original specimen to identify and quantify the presence of a specific drug or drug metabolite. 

confirmatory validity test. A second test performed on a different aliquot of the original

specimen to support or deny the initial validity test result. 

conjugate. A compound produced by the chemical joining of at least two other compounds. 

creatinine. An endogenous substance appearing in the urine, commonly used to estimate

kidney functioning. 

cutoff concentration or level. The measurement used to establish and report a specimen as

negative or positive. 

deconjugate. The breaking down of a substance into the original compounds. 

dilute specimen. A urine specimen whose creatinine is less than 20.0 mg/dL, but equal to or

greater than 2.0 mg/dL and whose specific gravity is less than 1.0030, but equal to or greater

than 1.0010. 

diversion (of prescribed medications). The act of selling or giving away prescribed medications

instead of taking them as prescribed. 

initial drug test. A test to differentiate a negative specimen from one that requires further

testing for drugs or drug metabolites. Also called a screening test. 
Clinical Drug Testing in Primary Care

78 

invalid result. The result reported when a scientifically supportable analytical test result

cannot be established for a specimen.
 

matrix. The biological medium tested for the presence of drugs or drug metabolites.
 

Medical Review Officer (MRO). A licensed physician who reviews, verifies, and reports a

specimen test result in regulated workplace programs. 

metabolite. A compound produced by enzymatic or chemical means while in the body, usually to

a more water soluble form for easy excretion.
 

negative test result. The result reported by a laboratory when a specimen contains a drug or

drug metabolite less than a prespecified cutoff level or concentration. 

pharmacogenomic. The genetic factors that influence an organism’s response to or metabolism

of a drug or a medication. 

point-of-care test (POCT). A drug or validity test conducted at the collection site to obtain an

initial or screening result on whether a specimen contains a drug or drug metabolite or is not a

valid specimen. Also called onsite, point-of-service, or point-of-collection test. 

positive test result. The result reported by a laboratory when a specimen contains a drug or

drug metabolite greater than or equal to a prespecified cutoff level or concentration. 

sample. A representative portion of a specimen or quality control material used for testing. 

specimen. Fluid or tissue derived from the body collected for testing. 

substituted specimen. A specimen that has been submitted in place of the patient’s urine, either

as evidenced by creatinine and specific gravity values that are outside the physiologically

producible ranges of human urine or is another person’s urine. 
79 

Appendix F—Expert Panel
 

Louis Baxter, M.D., Chair 

Executive Medical Director 

Professional Assistance Program of New 

Jersey

Princeton, New Jersey 

Lawrence S. Brown, Jr., M.D., M.P.H. 

Senior Vice President 

Addiction Research and Treatment 

Brooklyn, New York 

Paula Satterly Childs, Ph.D., D-ABFT

Director of Toxicology

Laboratory Corporation of America

Research Triangle Park, North Carolina 

Edward Cone, Ph .D . 

President 

ConeChem Research LLC 

Severna Park, Maryland 

Dennis J. Crouch, M.B.A. 

Associate Director for Sports Testing Services

Aegis Sciences Corporation

Nashville, Tennessee 

Martin Doot, M.D. (Deceased)

Medical Director 

Illinois Professionals Health Program

Des Plaines, Illinois 

Mahmoud A. ElSohly, Ph.D., BCFE, 

BCFM 

President 

ElSohly Laboratories, Inc.

Oxford, Mississippi 

M. P. George, M.S.

Laboratory Operations Director

Quest Diagnostics, Inc.

Schaumburg, Illinois 

Barbara L. Johnson, Esq.

Partner, Employment Department 

Paul Hastings

Washington, D.C. 

Donald Ian Macdonald, M.D., FASAM 

Chief Medical Officer 

Integrated Laboratory Services

Chestertown, Maryland 

Susan McCall, M.D., M.P.H. 

Medical Director 

Oregon Health Professionals Program

Tigard, Oregon 

Susan Neshin, M.D. 

Medical Director 

Jersey Shore Addiction Services

Asbury Park, New Jersey 

Kent Peterson, M.D. 

President 

Occupational Health Strategies, Inc.

Charlottesville, Virginia 

Gregory Rokosz, D .O ., J .D .

Senior Vice President 

Medical and Academic Affairs 

St. Barnabas Medical Center 

Livingston, New Jersey 

Michel A. Sucher, M.D., FACEP, FASAM 

Greenberg and Sucher, PC

Scottsdale, Arizona 

Robert E. Willette, Ph.D. 

President 

Duo Research, Inc. 

Eagle, Colorado 

81 

Appendix G—Consultants and Field 

Reviewers 

Consultants 

Peter David Friedmann, M.D., M.P.H. 

Assistant Professor 

Brown Medical School 

Departments of Medicine and Community

Health 

Rhode Island Hospital

Providence, Rhode Island 

Elizabeth A. Warner, M.D. 

Medical Director 

Ambulatory Services

Associate Professor 

Department of Internal Medicine

University of South Florida

Tampa, Florida 

Field Reviewers 

Paul L. Cary, M.S.

Director 

Toxicology and Drug Monitoring Laboratory

University of Missouri

Columbia, Missouri 

Nancy L. Hamilton, M.P.A., CAP, CCJAP

Chief Executive Officer 

Operation PAR

Pinellas Park, Florida 

Carolyn Hardin, M.P.A.

Director 

National Drug Court Institute

Alexandria, Virginia 

Jim Heit, M.T. 

Sterling Reference Laboratories

Tacoma, Washington 

Ron Jackson, M.S.W. 

Director 

Evergreen Treatment Services

Seattle, Washington 

Jason Kletter, Ph .D . 

President 

Bay Area Addiction Research and Treatment 

(BAART)

San Francisco, California 

83 

Appendix H—Acknowledgments
 

Numerous people contributed to the development of this Technical Assistance Publication

(TAP), including TAP expert panel members, consultants, and field reviewers (see Appendix F

and Appendix G, respectively). 

This publication was produced under the Knowledge Application Program (KAP), a Joint

Venture of The CDM Group, Inc., and JBS International, Inc. (JBS), for the Substance Abuse

and Mental Health Services Administration. 

Lynne MacArthur, M.A., A.M.L.S., served as the JBS KAP Executive Project Co-Director, and

Barbara Fink, RN, M.P.H., served as the JBS KAP Managing Project Co-Director. Other JBS

KAP personnel included Wendy Caron, Editorial Quality Assurance Manager; and Frances

Nebesky, M.A., Copy Editor. 

Technical Assistance Publications (TAPs) include:

TAPs 1–9, 25* These TAPs have been archived and are no longer available. 

TAP 10 Rural Issues in Alcohol and Other Drug Abuse Treatment 

TAP 11 Treatment for Alcohol and Other Drug Abuse: Opportunities for Coordination* 

TAP 12 Approval and Monitoring of Narcotic Treatment Programs: A Guide on the Roles of Federal and State 

Agencies* 

TAP 13 Confidentiality of Patient Records for Alcohol and Other Drug Treatment BKD156 

TAP 14 Siting Drug and Alcohol Treatment Programs: Legal Challenges to the NIMBY Syndrome BKD175 

TAP 15 Forecasting the Cost of Chemical Dependency Treatment Under Managed Care: The Washington State 

Study* 

TAP 16 Purchasing Managed Care Services for Alcohol and Other Drug Abuse Treatment: Essential Elements 

and Policy Issues* 

TAP 17 Treating Alcohol and Other Drug Abusers in Rural and Frontier Areas BKD174 

TAP 18 Checklist for Monitoring Alcohol and Other Drug Confidentiality Compliance* 

TAP 19 Counselor’s Manual for Relapse Prevention With Chemically Dependent Criminal Offenders (SMA) 

06-4217 

TAP 20 Bringing Excellence to Substance Abuse Services in Rural and Frontier America BKD220 

TAP 21 Addiction Counseling Competencies: The Knowledge, Skills, and Attitudes of Professional Practice 

(SMA) 12-4171 

TAP 21-A Competencies for Substance Abuse Treatment Clinical Supervisors (SMA) 12-4243 

TAP 22 Contracting for Managed Substance Abuse and Mental Health Services: A Guide for Public 

Purchasers BKD252 

TAP 23 Substance Abuse Treatment for Women Offenders: Guide to Promising Practices (SMA) 08-3929 

TAP 24 Welfare Reform and Substance Abuse Treatment Confidentiality: General Guidance for Reconciling 

Need to Know and Privacy BKD336 

TAP 26 Identifying Substance Abuse Among TANF-Eligible Families (SMA) 05-4089 

TAP 27 Navigating the Pathways: Lessons and Promising Practices in Linking Alcohol and Drug Services 

With Child Welfare* 

TAP 28 The National Rural Alcohol and Drug Abuse Network Awards for Excellence 2004, Submitted and 

Award-Winning Papers (SMA) 12-4183 

TAP 29 Integrating State Administrative Records To Manage Substance Abuse Treatment System Performance 

(SMA) 12-4268 

TAP 30 Buprenorphine: A Guide for Nurses (SMA) 09-4376 

TAP 31 Implementing Change in Substance Abuse Treatment Programs (SMA) 09-4377 

TAP 32 Clinical Drug Testing in Primary Care (SMA) 12-4668 

*Archived but available in electronic format at http://kap.samhsa.gov. 

TAPs may be ordered from SAMHSA’s Publications Ordering Web page at http://store.samhsa.gov. 

Or, please call SAMHSA at 1-877-SAMHSA-7 (1-877-726-4727) (English and Español). 
HHS Publication No. (SMA) 12-4668

Substance Abuse and Mental Health Services 

Administration

Printed 2012