1

Note: This manual is essentially the same as the 1997 HHS Medical Review Officer 

(MRO) Manual except for changes related to the new Federal Custody and Control 

Form (CCF). The appendix has also been deleted since the new Federal Custody and 

Control Form is available as a separate file on the website.

Medical Review Officer Manual for Federal Agency Workplace Drug 

Testing Programs for use with the new Federal Drug Testing Custody 

and Control Form (OMB Number 0930-0158, Exp Date: June 30, 2003)

This manual applies to federal agency drug testing programs that come under Executive 

Order 12564 and the Department of Health and Human Services (HHS) Mandatory 

Guidelines.

Table of Contents

Chapter 1. The Medical Review Officer (MRO)............................................................... 1

Chapter 2. Federal Drug Testing Custody and Control Form.......................................... 3

Chapter 3. The MRO Review Process ............................................................................ 3

A. Administrative Review of the CCF........................................................................... 3

I. State Initiatives and Laws ....................................................................................... 15

Chapter 4. Specific Drug Class Issues.......................................................................... 15

A. Amphetamines....................................................................................................... 15

B. Cocaine ................................................................................................................. 19

Chapter 5. Documentation and Recordkeeping ............................................................ 29

A. Recordkeeping ...................................................................................................... 29

Chapter 6. Additional MRO Responsibilities.................................................................. 30

A. Blind Quality Control Samples............................................................................... 30

Chapter 1. The Medical Review Officer (MRO)

An essential part of the drug testing program is the final review of results as required by 

the Mandatory Guidelines for Federal Workplace Drug Testing Programs initially 

published in the Federal Register on April 11, 1988 (53 FR 11970-11989) and revised in 

the Federal Register on June 9, 1994 (59 FR 29908-29931). A positive laboratory test 

result does not automatically identify an employee or job applicant as an illegal drug 

user. An individual with a detailed knowledge of possible alternative medical 

explanations is essential in performing this final review of results. The Medical Review 

Officer (MRO) fulfills this important function. 
2

An MRO is defined as a licensed physician who receives laboratory results, has 

knowledge of substance abuse disorders, and has appropriate medical training to 

interpret and evaluate an individual’s positive test result together with his or her medical 

history and any other relevant biomedical information. Only individuals holding either a 

Doctor of Medicine (M.D.) or Doctor of Osteopathy (D.O.) degree may serve as MROs 

for federally regulated programs.

The MRO may be an employee or a contractor for the Federal agency; however, the 

MRO must not be an employee or agent of or have any financial interest in the 

laboratory for which the MRO is reviewing drug testing results. Additionally, the MRO 

must not derive any financial benefit by having an agency use a specific drug testing 

laboratory or have any agreement with the laboratory that may be construed as a 

potential conflict of interest. The purpose of this requirement is to prevent any 

arrangement between a laboratory and an MRO that would prevent the MRO from 

reporting a problem identified with a laboratory’s test results or testing procedures. 

The MRO has the following responsibilities:

1. Determine that the information on the Federal drug testing custody and control 

form (CCF) is forensically and scientifically supportable; 

2. Interview the donor when required;

3. Make a determination regarding the test result;

4. Report the verified result to the Federal agency (employer); and 

5. Maintain records and confidentiality of the information.

It is recommended that MROs maintain a Standard Operating Procedure manual to 

ensure consistency and improve overall quality of the review process and participate in 

continuing education activities.

From initial requirements that an MRO be a licensed physician with knowledge of 

substance abuse disorders, practical requirements have evolved regarding the 

availability of various training programs. These programs ensure that MROs are familiar 

with current regulations and receive the latest information on interpreting drug testing 

results. Although there is no regulatory requirement for formal certification at the present 

time, the training courses offered by the various professional organizations have served 

a very important role in providing continuing education programs. 

The following professional organizations offer courses and information for licensed 

physicians who are interested in the MRO specialty:

American College of Occupational and Environmental Medicine (ACOEM)
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1114 North Arlington Heights Road

Arlington Heights, IL 60004

(847) 818-1800

American Society of Addiction Medicine (ASAM)

4601 North Park Avenue, Suite 101

Chevy Chase, MD 20815

(301) 656-3920

American Association of Medical Review Officers (AAMRO)

17 Running Brook Court

Durham, NC 27713

(919) 489-5407

The listing of these organizations is not an endorsement by the Federal government nor 

is attendance at one of their courses a regulatory requirement. 

Chapter 2. Federal Drug Testing Custody and Control Form

For specimens collected under the Guidelines, an Office of Management and Budget 

(OMB) approved Federal Drug Testing Custody and Control Form (CCF) must be used 

to document the collection of a specimen at the collection site. The CCF is available 

from a number of different sources (e.g., laboratories, collectors, MROs).

A sample of the CCF (OMB No. 0930-0158, Exp. Date: 6/30/2003) is on the SAMHSA 

web site (http://www.health.org/workpl.aspx). All discussions throughout this revised 

manual refer to this version of the CCF form.

The CCF has five copies that are distributed as indicated:

Copy 1. Laboratory Copy

Copy 2. Medical Review Officer Copy

Copy 3. Collector Copy

Copy 4. Employer Copy

Copy 5. Donor Copy

Chapter 3. The MRO Review Process

A. Administrative Review of the CCF

The MRO reviews the MRO Copy of the CCF, or if not available, a legible copy of any 

copy signed by the donor, which was received directly from the collection site. The MRO 

ensures that:

1. An OMB-approved CCF was used for the specimen collection.
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2. There is a specimen ID number on the top of the form along with the name and 

address of the laboratory testing the specimen.

3. Step 1 has all the required information (i.e., employer name and address, MRO 

name, address and phone number, donor SSN or other ID number, reason for 

the test, tests to be performed, collection site information).

4. The collector marked one of the temperature boxes, one of the specimen 

collection boxes, and the observed collection (if it was an observed collection) in 

Step 2 on the CCF.

5. The collector provided his or her printed name, a signature, date and time for the 

collection, and a comment (if appropriate) on the "Remarks" line in Step 2 on the 

CCF. The collector also provided the specific name of the delivery service that 

was used to transfer the specimen to the laboratory.

Apppears to be adulterated). The identification of these types of problems are for 

informational use by the laboratory and the MRO and, generally by themselves, are 

insote: The collector must use the "Remarks" line in Step 2 to identify any problem that 

may have occurred during the collection (e.g., donor refused to sign the donor 

statement on Copy 2 of the CCF, temperature of the specimen was outside the 

acceptable range and a second direct observed collection was conducted, why a 

specimen was not collected, why an observed collection was conducted, specimen 

apufficient to cancel the test. 

6. Step 5 on the CCF gives the donor identifying information (i.e., printed name, 

signature, date signed, daytime phone number, business phone number, and 

date of birth).

The MRO reviews Copy 1 of the CCF that is received from the testing laboratory. 

Note: A laboratory may transmit a result (negative or non-negative) to an MRO by either 

faxing the completed Copy 1 or transmitting a scanned image of the completed Copy 1 

by computer. A fax or scanned image of a completed Copy 1 is sufficient, by itself, for 

reviewing a negative result. For a non-negative result, the laboratory must send a hard 

copy of a completed Copy 1 to the MRO before the MRO can report the result to the 

employer.

Copy 1 is similar to Copy 2, but has the following additional information:

1. An accession number, if assigned by the laboratory, appears on the top of 

Copy 1 along with the specimen ID number.

2. The accessioner at the laboratory completed Step 4 (i.e., the accessioner 

provided a printed name and signature, indicated whether the primary 

specimen bottle seal was or was not intact, and indicated to whom or where 

the specimen bottle was released). 

3. Step 5a indicates the test result (i.e., the test result for a single specimen or 

the test result for the primary specimen (Bottle A) from a split specimen 

collection) and has the printed name and signature of the certifying scientist 
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and date signed. There may also be a comment on the "Remarks" line if the 

laboratory identified a problem with the specimen. The "Test Lab" line must 

also be completed if the test laboratory is different than the name appearing 

on the top of Copy 2.

Note: A comment on the "Remarks" line may identify either an administrative or a 

technical problem when the specimen was received or during the testing process (e.g., 

the seal on the primary specimen bottle was broken upon receipt, why the laboratory 

reported the specimen as adulterated or substituted, why the specimen was rejected 

for testing, why the laboratory reported an "Invalid Result"). The MRO must consider 

these comments when making a determination.

Note: Many laboratories also provide a separate computer generated report that gives 

much of the same information contained on Copy 1 of the CCF.

Note: If Copy 1 and Copy 2 are complete, it would appear that the collector followed 

the required collection procedure and the laboratory correctly tested and reported the 

test result.

If the MRO finds that the laboratory made an administrative error on Copy 1 or failed to 

identify an administrative error made by the collector, the MRO must contact either the 

collector or the laboratory (whichever made the administrative error) to determine if the 

collector or the laboratory can provide a Memorandum For Record (MFR) to 

recover/correct the administrative error. 

1. If the laboratory or the collector provides an MFR to recover/correct the 

administrative error, the MRO reports the verified result (i.e., whether the 

analytical test result was determined to be negative, positive, adulterated, 

substituted, or invalid result) to the employer and retains the MFR as part of the 

records associated with the testing of the specimen.

2. If the laboratory or the collector cannot

Note: When an MRO reports a "Test Canceled" result because the MRO believes that 

the administrative error has had a significant impact on the validity of the collection and 

testing process, it is the employer’s decision whether or not to immediately collect 

another urine specimen from the donor. Certain tests, such as, pre-employment, return 

to duty, require having a valid negative drug test result. 

provide an MFR to recover/correct the 

administrative error and the MRO believes that the administrative error has a 

significant impact on the validity of the entire collection and testing process, the

MRO may make and report a "Test Canceled" determination. If the MRO 

believes the administrative error does not have a significant impact on the 

validity of the collection or testing process, the MRO may report the verified 

result (i.e., whether the analytical test was determined to be negative, positive, 

adulterated, substituted, or invalid result) and must describe the administrative 

error that could not be recovered/corrected. 
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B. Technical Review of Single Specimen or Primary (Bottle A) Specimen Test 

Result

Note: It is assumed that the copies of the CCF were complete and all the information 

was accurate, except in some cases when the laboratory reports a "Rejected for 

Testing" result.

A specimen is defined to be:

1. Dilute if the creatinine is < 20 mg/dL and

2. Substituted (i.e., the specimen does not exhibit the clinical signs or 

characteristics associated with normal human urine) if the creatinine 

concentration is < 5 mg/dL 

the specific gravity is < 1.003, unless 

the criteria for a substituted specimen are met.

and

3. Adulterated if the nitrite concentration is > 500 g/mL.

the specific gravity is < 1.001 or > 1.020.

4. Adulterated if the pH is < 3 or > 11.

5. Adulterated if an exogenous substance (i.e., a substance which is not a normal 

constituent of urine) or an endogenous substance at a higher concentration than 

normal physiological concentration is present in the specimen.

When the laboratory reports a:

Negative Result

The MRO makes a "Negative" determination, completes Step 6 on Copy 2 of the CCF, 

and reports the "Negative" result to the employer.

If a laboratory also marked the dilute box, the MRO verifies the test result as "Negative," 

marks the dilute box, and informs the employer that the next time the donor is selected 

for a drug test the employer may require the specimen to be collected under direct 

observation because the specimen was dilute. 

Note: A comment indicating that the specimen was dilute does not affect the validity of a 

"Negative" test result.

Positive Result

The MRO interviews the donor. If the donor is unable to provide a valid alternative 

medical explanation, a positive laboratory test result is determined as a "Positive" by the 

MRO. If the donor provides a valid alternative medical explanation, the MRO reports the 

test result as "Negative." The MRO completes Step 6 on Copy 2 of the CCF and reports 

the appropriate result to the employer. 

If a laboratory also marks the dilute box, the MRO reports the verified test result (i.e., 

either "Positive" or "Negative"), marks the dilute box, and informs the employer that the 
7

next time the donor is selected for a drug test the employer may require the specimen to 

be collected under direct observation because the specimen was dilute.

Rejected for Testing Result

A laboratory will report a "Rejected For Testing" result and give the reason for rejecting 

the specimen when either of the following circumstances occur:

1. The specimen is not tested because a fatal flaw was identified when the 

specimen was accessioned (e.g., the specimen bottle seal was not intact upon 

receipt by the laboratory, the specimen ID number on the specimen bottle does 

not match the specimen ID number on the CCF, the specimen bottle contained 

insufficient volume, the specimen in Bottle A had a different appearance than the 

Bottle B specimen).

2. The specimen test result is not reported because the collection site was unable 

to provide a Memorandum for Record to correct/recover a flaw identified on the 

CCF or on the specimen bottle label/seal (e.g., the collector could not recall 

actually measuring the specimen temperature and had not checked the 

temperature box).

Note: If the collection site provides an MFR to correct/recover a flaw, the laboratory 

does not report a "Rejected for Testing" result but reports a "Negative" or "Positive" 

result as appropriate and a copy of the MFR is provided to the MRO when the test 

results are reported.

A "Rejected for Testing" result is determined by the MRO as a "Test Canceled" result. 

The MRO completes Step 6 on Copy 2 of the CCF and reports a "Test Canceled" result 

along with the reason for the cancellation to the employer. The MRO must also inform 

the employer that an immediate collection of another specimen is permitted, if the 

employer needs a "Negative" drug test result (e.g., pre-employment, return to duty, and 

follow-up tests require a "Negative" result). 

Adulterated or Substituted Result

Adulteration refers to a donor’s attempt to externally add something to his or her urine 

specimen in an attempt to affect the drug test. There are several products sold through 

the internet and advertised in drug culture magazines for this intended purpose.

Substitution refers to a donor’s attempt to replace his or her urine specimen with "clean" 

urine, synthetic urine, water, or other fluid during the collection procedure. 

An "Adulterated" or "Substituted" result is determined by the MRO as a "Refusal to 

Test." The MRO completes Step 6 on Copy 2 of the CCF and reports a "Refusal to 

Test" result along with the reason to the employer. 

Note: When a specimen is reported adulterated or substituted, the laboratory does not 
8

report a "Positive" drug test result even though the laboratory may have conducted and 

completed the confirmatory test.

Note: When a specimen appears to have an interferant that prevents the detection of 

the drug/metabolite in the confirmatory test and there is significant reduction or no 

recovery of the internal standard even after multiple extraction attempts, the laboratory 

may consult with the MRO and send the specimen to another HHS certified laboratory 

that has the capability of conducting scientifically suitable validity tests to identify the 

interfering substance/adulterant. If this process does not identify the interferant, the 

second laboratory will report an "Invalid Result."

Invalid Result

A laboratory will report an "Invalid Result" when either of the following circumstances 

occur:

1. The specimen is unsuitable for testing (e.g., physical appearance of the 

specimen is unacceptable and may affect the ability to analyze the specimen);

2. Valid initial drug test results cannot be obtained (e.g., a laboratory is unable to 

obtain a valid initial test result for each initial test and cannot specifically identify 

the cause); or

3. An unknown substance interferes with the confirmatory test.

The MRO must interview the donor to determine if the donor can provide any possible 

reason why the specimen could not be properly tested by the laboratory (e.g., medical 

illness, prescription medications, health food supplements).

Note: Tolectin® (Tolmetin - a non-steroidal anti-inflammatory medication), Flagyl® 

(metronidazole - an antifungal and antibacterial agent), and Cipro® (ciprofloxacin - an 

antibacterial agent) are the only known prescription medications that may interfere with 

some immunoassay tests.

If the donor is unable to give an explanation, provides a valid prescription for one of the 

above medications, or denies having tampered with the specimen, the MRO completes 

Step 6 on Copy 2 of the CCF, reports a "Test Canceled" result, and informs the 

employer that another specimen must be collected using a direct observed collection. 

The collection of a second specimen may possibly provide information needed to 

determine the reason why the first specimen was reported as "Invalid Result." If the 

second specimen collected using direct observation exhibits the same behavior as the 

first specimen, the MRO again reports the result for the second specimen as "Test 

Canceled" and recommends to the employer that no further action is required because 

the donor is either taking a valid prescription medication that interferes with the drug test 

or there is some unknown endogenous substance present in the donor’s urine that 

prevents getting a valid drug test result.

C. Interview Donor
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For the situations described above that require the MRO to interview the donor, the 

MRO contact and interview with the donor must include the following steps:

1. The MRO or an assistant makes the initial contact with the donor as soon as 

possible after receiving the result from the laboratory. There are no specific 

regulatory time lines, but the first attempt to contact the donor is usually within 24 

hours after receiving either the electronic transmission (if there is one) or the 

hard copy of the CCF (Copy 2) from the laboratory.

2. The MRO or an assistant makes a positive identification of the donor when the 

donor is actually contacted (e.g., asks the donor to provide his or her SSN).

Note: An assistant to the MRO may make the initial contact with the donor. This initial 

contact is useful since it is often time consuming to locate a donor, especially if the 

donor travels frequently or the donor’s phone number is incorrect. The assistant’s role 

must be limited to locating and making the initial contact with the donor. Once the donor 

is contacted and his or her identification is verified, the MRO must continue the 

interview.

3. The MRO tells the donor, before obtaining any information, that any confidential 

medical information provided by the donor during the review process may be 

disclosed to the employer.

4. The MRO informs the donor that the laboratory has reported either a "Positive" 

drug test result or an "Invalid Result."

5. The MRO asks the donor if there is any possible explanation for either result.

Note: If the donor voluntarily admits to illegal drug use consistent with the test results, 

the MRO must advise the donor that a verified "Positive" result will be reported to the 

employer.

Note: If the donor claims to have used a legally prescribed medication or the drug use 

was associated with a legitimate medical procedure, the MRO must require the donor to 

provide the appropriate documentation (e.g., medical record, doctor's report, copy of a 

prescription). The MRO must give the donor a deadline for submitting the medical 

information. 

6. If a split specimen was collected and the Bottle A specimen was reported 

"Positive," the MRO informs the donor of the opportunity to request that the split 

specimen be tested. If the donor requests the split specimen to be tested, the 

MRO directs the laboratory to send Bottle B to another certified laboratory for 

confirmatory testing.

7. If the information submitted by the donor is or is not sufficient to support the 

legitimate medical use of a prescription medication that would cause the 

"Positive" test result for the drug reported by the laboratory, the MRO reports the 

result to the employer as a verified "Negative"or "Positive," respectively, and 

completes Step 6 on Copy 2 of the CCF.
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Note: Ideally, the MRO is always able to contact the donor, obtain the appropriate 

information, and make a determination during or immediately after the interview. 

However, this is not always the case. Occasionally, the MRO is unable to contact the 

donor for various reasons (e.g., the donor has moved, no longer works for the employer, 

or was a job applicant and has moved).

The MRO may verify a positive test as "Positive" without having communicated directly 

with the donor (i.e., a non-contact determination) for the following reasons:

The donor expressly declines the opportunity to discuss the test result;

1. The MRO, after making all reasonable efforts, has not been able to contact the 

donor within 14 days of the date on which the MRO receives the "Positive" test 

result from the laboratory; or

2. The employer has contacted the donor and instructed the donor to contact the 

MRO, but the donor has not contacted the MRO within 5 days after being 

contacted by the employer.

The MRO must establish guidelines as to what constitutes a reasonable effort to contact 

the donor and must document all attempts that were made to contact the donor. When 

contacting the employer regarding the effort made to contact the donor, the MRO may 

not reveal the test result or any information about the drug test. The employer must 

confidentially direct the donor to contact the MRO within 5 days and must inform the 

MRO once the donor has been so instructed or if unable to contact the donor. 

D. Retest Request

Single Specimen or Primary (Bottle A) Specimen

Before making a determination on a "Positive" test result, only the MRO is permitted to 

request a retest of a single specimen or the primary (Bottle A) specimen from a split 

specimen collection if there is any question regarding the accuracy or validity of the test 

result. The MRO’s request must be based on a review of technical information (provided 

by the laboratory or donor) that makes the MRO believe that the result may be 

scientifically insufficient and, therefore, believes that a retest would be useful before

making the determination.

Note: The MRO can request that the retesting of the original specimen be performed by 

the same laboratory or that an aliquot of the single specimen be sent for a retest to 

another certified laboratory. The Mandatory Guidelines are silent with respect to who 

chooses the second laboratory. The only requirement is that the second laboratory is 

certified by HHS whether it is chosen by the agency/employer, donor, MRO, or the first 

laboratory.

Note: It is unacceptable for an MRO to automatically request a retest on every 

specimen. There must be a sound justifiable scientific basis for each retest request.
11

Note: To ensure that a specimen is available if a retest is requested either by an MRO 

or by an official administrative or judicial proceeding, HHS requires laboratories to place 

all specimens confirmed positive in properly secured frozen storage for a minimum of 

one year. This is generally a sufficient amount of time to allow for a retest to occur; 

however, the time may be extended beyond one year by either the employer or an 

administrative/judicial official to allow completion of any litigation/arbitration that may be 

ongoing with the donor. If split specimens were collected, the laboratory keeps both 

specimen bottles frozen for one year. If Bottle B was sent to another laboratory for 

confirmatory testing, that laboratory retains Bottle B in frozen storage for one year.

The MRO must request the retest of a single specimen or the primary (Bottle A) 

specimen in writing (i.e., a memorandum or letter format). The written request may be 

mailed, faxed, or electronically sent to the laboratory where the specimen was tested 

and must contain the following information:

1. MRO name and address (use MRO letterhead);

2. Laboratory name and address (i.e., Laboratory A) where original analysis was 

performed;

3. Specimen I.D. Number (i.e., number on the Custody and Control Form);

4. Laboratory Accession Number (i.e., the number assigned by Laboratory A to the 

specimen when it was accessioned); and

5. Request confirmatory retest for the drug/metabolite reported by Laboratory A.

Note: If the retest is to be performed at a different certified laboratory (Laboratory B), the 

MRO also includes the name and address of this certified laboratory. Laboratory B may 

be selected by the MRO, the employer in its contract with the laboratory that tested the 

single specimen (Laboratory A), or by the donor.

Note: The result of a retest of a single specimen is reported by the laboratory using an 

appropriate laboratory report form to the MRO.

Split (Bottle B) Specimen

After making the determination that the primary Bottle A specimen is "Positive," the 

MRO must inform the donor of his or her right to request an analysis of the split (Bottle 

B) specimen. The donor’s request to have the split specimen tested must be made 

through the MRO. Although the time allowed for a retest request may vary, the donor is 

given a maximum of 72 hours to initiate the request. This will ensure that the analysis of 

the split specimen is performed in a timely manner.

The MRO must request the testing of the split (Bottle B) specimen in writing (i.e., a 

memorandum or letter format). The written request may be mailed, faxed, or 

electronically sent to the laboratory where the specimen was tested and must contain 

the following information:
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1. MRO name and address (use MRO letterhead);

2. Laboratory name and address (i.e., Laboratory A) where analysis of the primary 

(Bottle A) specimen was performed;

3. Specimen I.D. Number (i.e., number on the Custody and Control Form);

4. Laboratory Accession Number (i.e., the number assigned by Laboratory A to the 

specimen when it was accessioned);

5. Request confirmatory test for drug/metabolite reported by Laboratory A; and

6. Name and address of the laboratory (i.e., Laboratory B) selected to test the 

Bottle B specimen.

Note: Laboratory B may be selected by the MRO, the employer in its contract with 

Laboratory A, or by the donor. 

Note: Laboratory B will report the result for the split (Bottle B) specimen on Copy 1 of 

the CCF to the MRO. The MRO reports the result to the employer and the donor. 

E. Retest Result

Single Specimen or Primary (Bottle A) Specimen

If the retesting of the original specimen fails to reconfirm the original laboratory result, 

the MRO will report the result as "Negative" to the employer.

Note: Since this retest was performed because the MRO had concerns regarding the 

validity of the positive test result reported by the laboratory, the MRO cannot make a 

determination before the retest result is reported to the MRO by the laboratory.

Note: When a retest does not reconfirm the presence of a drug, the MRO must contact 

the appropriate regulatory office. The regulatory office will conduct an investigation to 

determine the reason for not reconfirming the presence of the drug and to ensure that 

appropriate corrective action is implemented.

Split (Bottle B) Specimen

If the testing of the split (Bottle B) specimen reconfirms the presence of the drug/drug 

metabolite, the MRO verifies the result for the split (Bottle B) specimen as 

"Reconfirmed" on Copy 2 of the CCF.

If the testing of the split (Bottle B) specimen fails to reconfirm the result reported by the 

laboratory that tested the primary (Bottle A) specimen, the MRO verifies the result as 

"Failed to Reconfirm"along with the reason on Copy 2 of the CCF 

Note: Since the "Positive" result for the primary (Bottle A) specimen had been reported 

to the employer by the MRO, the employer will be required to reverse any personnel 

action that may have been taken against the donor. Additionally, the donor reenters the 

group of individuals subject to random testing as if the test had not been conducted.
13

Note: The Federal agency must notify the appropriate regulatory office whenever a 

"Failed to Reconfirm" result has occurred on a split (Bottle B) specimen. The regulatory 

office will investigate the "Failed to Reconfirm" result and attempt to determine the 

reason for the inconsistent results. HHS will report its findings to the Federal agency 

including recommendations and/or actions taken to prevent the recurrence of the 

"Failed to Reconfirm" result.

There is a technical problem that occasionally occurs when Laboratory B retests an 

aliquot of a single specimen or tests a split (Bottle B) specimen that had been reported 

"Positive" by Laboratory A. Laboratory B is unable to reconfirm the presence of the drug 

or metabolite reported by Laboratory A because it uses a different analytical procedure 

and/or instrumentation. These differences occasionally prevent a Laboratory B from 

reconfirming the presence of a drug or metabolite because the analytical results do not 

satisfy all the criteria required to make a positive identification. 

Note: If Laboratory B believes that the drug or metabolite is present in the aliquot of the 

single specimen or the split (Bottle B) specimen that was received from Laboratory A, 

but cannot reconfirm the presence of the drug or metabolite, Laboratory B, after 

consultation with the MRO, may send the aliquot of the single specimen or the split 

(Bottle B) specimen to Laboratory C for confirmatory testing. The MRO may also 

request Laboratory A to send another aliquot of the single specimen to Laboratory C if 

there is an insufficient quantity of urine remaining in the aliquot of the single specimen 

tested at Laboratory B. Laboratory C should be selected such that it uses a confirmation 

method more similar to that used by Laboratory A. 

F. Report Verified Result to Employer

The MRO may report all verified (negative and non-negative) results to the 

agency/employer by either faxing a completed Copy 2, transmitting a scanned image of 

a completed Copy 2, or faxing a separate report using a letter/memorandum format. A 

verified result may not be reported to the employer until the MRO has completed the 

review process. The MRO must send to the agency/employer a hard copy of either the 

completed Copy 2 or the separate letter/memorandum report for all non-negative 

results.

Note: If the MRO uses a letter or memorandum format, it must include, at a minimum, 

the following: donor name and/or SSN, specimen I.D. number from the CCF, the verified 

test result (if positive, list specific drug(s)), the MRO’s printed name and signature, and 

the date the determination was made. The MRO may list results for several specimens 

on one memorandum or letter. The MRO report may include relevant comments 

provided by the collector and/or laboratory on the CCF as well as other information, 

such as, documentation of attempts to contact the donor or a statement of the donor's 

refusal to cooperate with the medical review process. The MRO may add any 

information provided by the donor (especially at the donor's request) to the verified 

result report. Such additional information must not, however, reveal specific confidential 
14

medical information. 

G. Full Documentation Package

A donor or employer will occasionally request the testing laboratory to provide a 

complete package of analytical data, chain of custody records, and other administrative 

documents associated with the testing of a particular specimen. This package is 

generally referred to a "full documentation package"

The request must always be submitted to the laboratory through the MRO. A full 

documentation package must include copies of the batch test results that contain the 

test result for the donor’s specimen, internal and external chain of custody documents 

for the batch of specimens that contain the donor’s specimen, and any other relevant 

information pertaining to the testing of the donor’s specimen.

Although each documentation package is different, it must contain all the information 

needed to determine if the test result reported by the laboratory is, in fact, scientifically 

and forensically supportable. The MRO is encouraged to contact the laboratory to 

discuss the information contained in the documentation package prior to sending it to 

the donor or employer. The MRO may find that additional information (e.g., a description 

of the laboratory’s chain of custody procedures, a description of the laboratory’s quality 

assurance program) would be helpful in reviewing the full documentation package.

H. Occupational and Public Safety

Executive Order 12564 used the term "illegal drugs" to refer to any controlled substance 

that was included in Schedule I or II of the Controlled Substances Act. The Executive 

Order also stated that the term illegal drugs "does not mean the use of a controlled 

substance pursuant to a valid prescription or other uses authorized by law."

Note: The purpose of this policy is to ensure that a Workplace drug testing program 

does not intentionally identify an individual who is receiving legitimate medical care and, 

thereby, provides confidential medical information to an employer or anyone else. 

There is, however, a public safety issue associated with information that a donor may 

provide to an MRO during the review of a drug test result. That is, the donor may be 

taking a legal prescription medication as treatment for a medical condition and the 

medication may have possible side effects that may impair the mental and/or physical 

abilities required for the performance of potentially hazardous tasks (e.g., driving a car 

or truck, operating machinery).

If the side effects of a legitimately prescribed medication have a possible impact on the 

safety aspects of the work performed by a donor, the MRO must decide what must be 

done with the information. Although the Guidelines require an MRO to verify a drug test 

result as a negative result if the donor has legally taken a prescription medication, it is 

recommended that the MRO contact the prescribing physician to discuss the possible 
15

impact that the medication may have on the safety aspects of the work performed by 

the donor. Additionally, some occupations have restrictions that prohibit an individual 

from taking specific medications which may, otherwise, be allowable for other 

occupations. In these instances, the MRO may inform the individual responsible for 

certifying that the donor is qualified to perform that job that the donor is taking a 

medication that is restricted for an individual in that occupation or that the medication 

may affect the individual’s ability to perform a safety sensitive occupation.

I. State Initiatives and Laws

State initiatives and laws which make available to an individual a variety of illicit drugs 

by a physician’s prescription or recommendation do not make the use of these illicit 

drugs permissible under the Federal Drug-Free Workplace Program. These State 

initiatives and laws are inconsistent with Federal law and put the safety, health, and 

security of Federal workers and the American public at risk.

The use of any substance included in Schedule I of the Controlled Substance Act, 

whether for non-medical or ostensible medical purposes, is considered a violation of 

Federal law and the Federal Drug-Free Workplace Program. These drugs have no 

currently accepted medical use in treatment in the United States and their uses are 

inconsistent with the performance of safety-sensitive, health-sensitive, and securitysensitive positions, and with other testing circumstances.

Note: Medical Review Officers shall not

Chapter 4. Specific Drug Class Issues

accept a prescription or the verbal or written 

recommendation of a physician for a Schedule I substance as a legitimate medical 

explanation for the presence of a Schedule I drug or metabolite in a Federal 

employee/applicant specimen.

A. Amphetamines

1. Background

Amphetamine and methamphetamine are substances regulated under the Controlled 

Substances Act (CSA, 21 U.S.C. § 801 et seq.), and implementing regulations as 

Schedule II stimulants (see 21 CFR § 1308.12(d)). Schedule II substances have 

legitimate medical uses, but also have a high potential for abuse. Both drugs have been 

used for treating attention deficit disorder in children, obesity, and narcolepsy. 

Amphetamine and methamphetamine are central nervous system stimulants. A single 

therapeutic dose often enhances attention and performance, but exhaustion eventually 

occurs and performance deteriorates as the effects wear off. Frequently, repeated highdose use produces lethargy, exhaustion, mental confusion, and paranoid thoughts.
16

Tolerance can develop to the effects of amphetamine and methamphetamine. A typical 

therapeutic dose is five milligrams. Individuals who abuse these drugs are reported to 

inject up to one gram in a single intravenous dose. Physical dependence is modest. 

Lethargy, drowsiness, hyperphagia, vivid dreams, and some mental depression may 

persist for a few days to several weeks after abrupt termination of repeated high doses.

Amphetamine and methamphetamine are usually taken orally as tablets or capsules. 

Abusers inject the drugs intravenously, sometimes take them by intranasal "snorting," 

and by smoking. Absorption from the gastrointestinal tract is good and they are 

distributed throughout the body.

2. Metabolism and Excretion

Nearly half of a methamphetamine dose is recovered from urine unchanged. A small 

percentage is demethylated to amphetamine and its metabolites. The excretion rate of 

methamphetamine is also increased when urine is acidic.

Amphetamine is excreted as both unchanged amphetamine and as hydroxylated 

metabolites. Typically, about one-quarter of an administered dose is excreted as 

unchanged amphetamine, but this varies widely with urinary pH; the drug stays in the 

body longer when urine is alkaline, allowing reabsorption and thus allowing more of it to 

be metabolized. In 24 hours, about 80 percent of a dose will be excreted if urine is 

acidic, while less than half is excreted if urine is alkaline.

A single therapeutic dose of amphetamine or methamphetamine can produce a positive 

urine for about 24 hours depending upon urine pH and individual metabolic differences. 

High dose abusers may continue to generate positive urine specimens for 2 to 4 days 

after last use.

Methamphetamine and amphetamine exist in two isomeric structural forms known as 

enantiomers. Enantiomers are non-superimposable mirror images. The two isomers of 

each substance are designated as d- (dextro) and l- (levo), indicating the direction in 

which they rotate a beam of polarized light. As do many pharmacological enantiomers, 

the d- and l- isomers have distinct pharmacological properties. In this case, the disomer of each substance has a strong central nervous system stimulant effect while the 

l- isomer of each substance has primarily a peripheral action. 

Generally, the methamphetamine/amphetamine result reported by the laboratory does 

not indicate which enantiomer is present because the laboratory procedure is set up to 

only identify and quantify the methamphetamine/amphetamine that is present. In order 

to determine which enantiomer is present, an additional analysis must be performed.

The enantiomer identification may be useful in determining if a donor has been using a 

Vicks Inhaler®, a prescription medication, or abusing an illegal drug. The presence of 

the l- isomer of either amphetamine or methamphetamine does not by itself rule out 
17

illegal use.

Illegally manufactured amphetamine and methamphetamine often contain significant 

amounts of the l- isomer of each substance. This depends on the starting materials 

used by the clandestine laboratories. 

The following prescription medications contain d-amphetamine or racemic d,lamphetamine (i.e., equal amounts of d- and l-amphetamine):

Adderall®

Benzedrine®

Biphetamine® 

Dexedrine® 

Durophet® 

Obetrol® 

The following prescription medication contains d-methamphetamine:

Desoxyn® (Gradumet®)

The following substances are known to metabolize to methamphetamine (and 

amphetamine):

Benzphetamine (Didrex®)

Dimethylamphetamine

Famprofazone

Fencamine

Furfenorex

Selegiline (Deprenyl, Eldepryl®)

The following substances are known to metabolize to amphetamine:

Amphetaminil

Clobenzorex (Dinintel®, Finedal®)

Ethylamphetamine

Fenethylline (Captagon®)

Fenproporex (Tegisec®)

Mefenorex (Pondinil®)

Mesocarb

Prenylamine

Note: These lists are not all inclusive.

3. Interpreting Laboratory Result

The donor provides the following response:

a. Claims to have been taking a prescription medication.

(1) The MRO requests the donor to provide a copy of the prescription or the 

sample bottle with the appropriately labeled prescription.
18

Note: The prescription must be for a drug that contains either amphetamine, 

methamphetamine, or a substance that can metabolize to amphetamine or 

methamphetamine. If the prescription does not satisfy this requirement, the drug 

in the prescription provided by the donor is not a valid medical explanation for the 

positive amphetamine result and the "Positive" laboratory result is verified as a 

"POSITIVE." 

Note: If the donor had completed taking the prescribed medication by the time he 

or she is contacted, the donor may no longer have the prescription bottle. When 

this occurs, the donor must provide a copy of the medical record that documents 

the valid medical use of the drug during the time of the drug test. There may be a 

need to contact the prescribing physician or the pharmacist who filled the 

prescription to verify the information provided by the donor.

Note: If a donor has been taking a prescription medication that contains 

methamphetamine or amphetamine for a long time, there must be appropriate 

justification for their long term use because of the high potential for abuse. The 

MRO must contact the prescribing physician to express concern that the 

continued use of the medication may present a significant safety problem for the 

donor while on the medication.

Note: Selegiline is a brain monoamine oxidase inhibitor used in the adjunctive 

treatment of Parkinson’s disease and for depression. Selegiline is metabolized to 

l-methamphetamine and l-amphetamine. A d- and l- isomer differentiation will 

reveal the presence of only l-methamphetamine and l-amphetamine after the 

ingestion of Selegiline.

(2) If this alternative medical explanation is substantiated for a specimen 

containing only l-methamphetamine/l-amphetamine, the MRO must verify and 

report the result as a "Negative."

b. Claims to have used a Vicks Inhaler®.

(1) Since the Vicks Inhaler® contains l-methamphetamine, there is a possibility 

that a laboratory positive result could be reported for l-methamphetamine and/or

l-amphetamine.

(2) The MRO may request the laboratory to perform a d-, l- isomer differentiation.

Note: Although one would expect to see 100% l-methamphetamine following 

Vicks Inhaler® use, there may be a trace amount of d- isomer present because a 

very slight amount of d-methamphetamine may be present as a contaminant in 

the Vicks Inhaler® and a contaminant of the analytical procedure.

(3) After the laboratory conducts the isomer differentiation, if there is greater than 
19

80% l-methamphetamine, the results are considered to be consistent with Vicks 

Inhaler® use and the result is verified as a "Negative."

Note: This is a very conservative interpretation.

(4) If there is more than 20% d-methamphetamine present, the results indicate 

the use of some source other than the inhaler and the result is verified as a 

"Positive.

c. Claims to have used other over-the-counter medications.

(1) The MRO would verify the laboratory result as a "Positive."

Note: There are no over-the-counter medications, other than the Vicks Inhaler®, 

that contain either d- or l- methamphetamine or amphetamine. Although we know 

that some sympathomimetic amines can test positive on an immunoassay test, 

they will not be reported positive by the laboratory after conducting the 

confirmatory test; the confirmatory GC/MS test is specific for methamphetamine 

and amphetamine.

The NLCP requires that a specimen reported as a "Positive" for 

methamphetamine only (i.e., above the confirmatory test level of 500 ng/mL), it 

must also contain amphetamine (which is a metabolite of methamphetamine) at a 

concentration equal to or greater than 200 ng/mL. The amphetamine will not be 

reported as "Positive" by the laboratory unless its concentration exceeds the 500 

ng/mL confirmatory test level. In the case of a report stating only a 

methamphetamine positive, the MRO may contact the laboratory to verbally 

confirm that amphetamine was present between 200 and 500 ng/mL. 

d. Admits or denies using any substance illegally. The MRO verifies the result as a 

"Positive" for amphetamine and/or methamphetamine.

B. Cocaine

1. Background

Cocaine is an alkaloid from the coca plant, Erythroxylon coca. It usually is obtained as 

cocaine HCl, but those who smoke the drug prepare the "freebase" or "crack" form, 

chemically removing the HCl. This form better survives the high temperatures involved 

in smoking.

Cocaine is widely used in the United States, and unlike most other drugs, its prevalence 

of abuse continues to expand. 

Cocaine produces psychomotor and autonomic stimulation with a euphoric subjective 

"high." Larger doses may induce mental confusion or paranoid delusions, and serious 

overdoses cause seizures, respiratory depression, cardiac arrhythmias, and death.
20

Cocaine abusers, even if they do not use the drug at work, often report vocational 

impairment due to exhaustion; they use the drug until late at night. Among chronic 

users, exhaustion, lethargy, and mental depression appear, and the stimulant effect 

may seem progressively weaker. But the drug is highly reinforcing; repeated 

experiences with it tend to drive further episodes of self-administration. After repeated 

exposures, many patients say that although the drug no longer produces much of a 

"high," they are unable to abstain.

Short-term tolerance (tachyphylaxis) develops when several doses of cocaine are 

administered over a brief period. Reports of weaker "highs" with repeated use also 

suggest tolerance. However, animal studies show "reverse tolerance," with certain 

behavioral effects becoming stronger upon repeated administration. So the question of 

tolerance to cocaine remains an area for further research. Patients withdrawing from 

cocaine experience moderate lethargy and drowsiness, severe headaches, 

hyperphagia, vivid dreams, and some mental depression. These symptoms usually 

abate within a few days to a few weeks.

Cocaine usually is taken by one of three routes: intranasal "snorting" is the most 

common; its "freebase" or "crack" form of the drug is smoked, utilizing the pulmonary 

route; and intravenous injections.

2. Metabolism and Excretion

Cocaine is rapidly and extensively metabolized by liver and plasma enzymes. The major 

metabolite, benzoylecgonine, is more persistent; it usually is detected for 2 days after a 

single dose. Cocaine and benzoylecgonine are not significantly stored in the body; 

therefore, even after heavy, chronic use urine specimens will be negative when 

collected a few days after last use.

3. Interpreting Laboratory Result

The donor provides the following response:

a. Claims to have used a prescription medication or was given cocaine during a 

medical or dental procedure.

Note: There are no prescription medications that contain cocaine. However, the 

medical community uses TAC (tetracaine, adrenalin, cocaine) as a topical 

preparation prior to various surgical procedures and may use cocaine by itself as 

a topical vasoconstrictive anesthetic for various ear, nose, throat, and 

bronchoscopy procedures. If cocaine is used, the licensed physician performing 

the procedure would document its use in the donor’s medical record. Cocaine is 

structurally unique and does not resemble any of the other topical anesthetics, 

such as Novocain®, Xylocaine® (lidocaine), benzocaine, etc. Although these 

compounds have analgesic properties, there is no structural similarity to cocaine 

or its metabolite (benzoylecgonine).
21

(1) Request the donor to provide a copy of the medical record that documents 

the recent use of cocaine as a topical anesthetic.

(2) If this alternative medical explanation is substantiated, the MRO must verify 

and report the result as a "Negative."

Note: Keep in mind that the medical use must have occurred within 2 to 3 days 

prior to when the urine specimen was collected. Use at an earlier time will not 

cause a positive urine test.

b. Claims passive inhalation of crack cocaine.

(1) Allow the donor to describe the circumstances pertaining to how and when 

the passive exposure occurred.

(2) Passive inhalation is not an alternative medical explanation for the presence 

of benzoylecgonine in the donor’s urine.

Note: A comprehensive study conducted at NIDA’s Addiction Research Center 

(E.J. Cone, D. Yousefnejad, M.J. Hillsgrove, B. Holicky, and W.D. Darwin. 

Passive Inhalation of Cocaine. J.Anal.Toxicol. 19:399-411(1995)) has 

demonstrated that individuals passively exposed to "crack" smoke did not 

produce a urine positive for cocaine using the established testing levels.

(3) MRO verifies and reports the result as a "Positive.

c. Claims to be ingesting "Health Inca Tea."

Note: In the early 1980s, health food stores were selling a tea under the 

tradename "Health Inca Tea." When it was discovered that this tea contained 

decocanized coca leaves with detectable amounts of cocaine present, the U. S. 

Food and Drug Administration banned the importation of this tea into the United 

States. Therefore, any tea being sold using the name "Health Inca Tea" should 

not contain any cocaine.

(1) Allow the donor to explain where and when the tea was purchased.

(2) Drinking "Health Inca Tea" is not an alternative medical explanation for the 

presence of benzoylecgonine in the donor’s urine.

(3) MRO verifies and reports the result as a "Positive."

d. Admits or denies using cocaine. The MRO verifies the result as a "Positive" for 

cocaine.

C. Marijuana
22

1. Background

Marijuana comes from the hemp plant, Cannabis sativa. The principal psychoactive 

agent in marijuana is delta-9-tetrahydrocannabinol (THC).

Marijuana produces a pleasant euphoria or "high," commonly followed by drowsiness. 

Intoxication temporarily impairs concentration, learning, and perceptual-motor skills. 

Thus, for at least 4-6 hours after a dose of marijuana, employees probably function with 

reduced abilities. Preliminary studies suggest that performance is impaired long after 

the acute subjective effects have ended. Experienced pilots in a flight simulator were 

impaired for at least 24 hours after a dose, long after the subjective "high" had 

disappeared. Functional impairments are less well understood in cases of prolonged, 

heavy marijuana use, because although THC accumulates in the body, behavioral and 

physiological tolerance also develops.

In addition to tolerance, a mild abstinence syndrome may follow abrupt termination of 

very high-dose, chronic marijuana use. Withdrawal signs include irritability, sleep 

disturbance, diminished appetite, gastrointestinal distress, salivation, sweating, and 

tremors. Marijuana abstinence syndromes are uncommon at the doses at which the 

drug is usually taken in this country.

2. Metabolism and Excretion

Marijuana is usually smoked; transpulmonary absorption rapidly gets psychoactive 

drugs to the brain. Since the drug also is absorbed from the gastrointestinal tract, 

although much more slowly, marijuana sometimes is eaten. THC leaves the 

bloodstream and is distributed into different parts of the body where it is metabolized, 

excreted, or stored. The THC that is stored in fatty tissue gradually reenters the blood 

stream at very low levels, permitting metabolism and eventual excretion. THC is 

metabolized extensively in the liver and the major metabolite is 11-nortetrahydrocannabinol -9-carboxylic acid (delta-9 THCA). 

The immunoassay procedures detect multiple metabolites of marijuana, while the 

GC/MS procedure specifically identifies and quantitates the delta-9 THCA metabolite. 

To be reported positive, a specimen must screen positive at or above the 50 ng/mL 

cutoff and have a concentration of the delta-9 THCA that is equal to or greater than the 

15 ng/mL confirmatory cutoff level. Considering these cutoffs, a person with no 

marijuana experience who smokes a single marijuana cigarette may be positive for 1-3 

days. But with repeated smoking, THC accumulates in fatty tissue; so frequent, chronic 

smokers slowly release THC over a longer time and may continue to produce 

detectable levels below the cutoff values for longer periods of time (depending upon the 

assay cutoff).

3. Interpreting Laboratory Result

The donor provides the following response:
23

a. Claims to have used a prescription or over-the-counter medication.

Note: Dronabinol is chemically synthesized delta-9- tetrahydrocannabinol (THC). 

It is available under the trade name Marinol® in 2.5, 5, or 10 mg soft gelatin 

capsules for oral administration. Marinol® may be used for stimulating appetite 

and preventing weight loss in patients with a confirmed diagnosis of AIDS and 

treating nausea and vomiting associated with cancer chemotherapy. Additionally, 

a few individuals have been permitted by a court order to use THC for the 

management of glaucoma. Patients that are prescribed Marinol® should be 

warned not to drive, operate complex machinery, or engage in hazardous 

activity.

Note: There are no other prescription or over-the-counter medications that 

contain cannabinoids or any other substances that might be identified as or 

metabolized to THC or its acid metabolite.

(1) Request the donor to provide a copy of the medical record or court order that 

would document the legal use of Marinol® or marijuana.

(2) If this alternative medical explanation is substantiated, the MRO must verify 

and report the result as a "Negative."

b. Claims passive inhalation or unknowing ingestion.

Note: Passive inhalation, unknowing ingestion (i.e., an inadvertent exposure to 

marijuana), or eating hemp seeds is frequently claimed as the basis for a positive 

urine test. Passive inhalation of marijuana smoke does occur and can result in 

detectable levels of THC and its metabolites in urine. Clinical studies have 

shown, however, that it is highly unlikely that a nonsmoking individual could 

unknowingly inhale sufficient smoke by passive inhalation to result in a high 

enough drug concentration in urine for detection at the cutoff levels used in the 

Federal program. Similarly, it is extremely difficult to achieve detectable levels 

through unknowing ingestion of hemp plant material (such as, leaves, stems) or 

eating food products containing hemp seeds. The studies also show that any 

measurable peak concentration in urine occurs within several hours after the 

exposure.

(1) Allow the donor to describe the circumstances pertaining to how and when 

the passive exposure, unknowing ingestion, or eating hemp seeds occurred.

(2) Generally, the circumstances will not approximate what would be needed to 

explain the presence of THC in the donor’s urine.

(3) MRO verifies and reports the result as a "Positive."
24

Note: Additionally, none of the reasons mentioned in b1 above constitute an 

alternative medical explanation.

c. Admits or denies using marijuana. The MRO verifies the result as a "Positive" for 

cannabinoids.

D. Opiates

1. Background

Opioids are a large class of analgesic drugs, the effects of which are stereospecifically 

antagonized by naloxone. Opiates refer to natural products derived from the juice of the 

opium poppy (loosely applied to morphine derivatives). The opium poppy flower is the 

source of the natural opiate prototype alkaloid, morphine. The opium poppy is also the 

source of the naturally occurring alkaloid codeine; codeine is also synthesized 

chemically for inclusion in medications available through prescription and over-thecounter. Heroin (or diacetylmorphine) is a semisynthetic opiate obtained by reacting 

natural morphine with acetic acid. Heroin has no legitimate medical uses in the United 

States and is only available illegally (DEA Schedule I).

Opioid intoxication may cause miosis, a dull facies, confusion or mental dullness, 

slurring of speech, drowsiness, partial ptosis, or "nodding" (the head drooping toward 

the chest and then bobbing up). 

Tolerance develops to opioid effects, and abusers escalate doses when possible. 

Physical dependence results in a moderate, nonlethal, "flu"-like abstinence syndrome 

with nausea, diarrhea, coryza, occasional vomiting, weakness, malaise, "gooseflesh," 

and mydriasis. All opiates are physically and psychologically addictive, and produce 

withdrawal symptoms that differ in type and severity. Flu-like symptoms are common 

during opiate withdrawal, e.g., watery eyes, nausea and vomiting, muscle cramps, and 

loss of appetite.

Heroin and morphine are usually injected, but may be smoked as opium once was, or 

"snorted" (insufflated) onto the nasal mucosa. 

Cognitive and psychomotor performance can be impaired by opiates, although the 

duration and extent of impairment depend on the type of opiate, the dose, and the 

experience and drug history of the user. Ingestion of low to moderate amounts produces 

a short-lived feeling of euphoria followed by a state of physical and mental relaxation 

that persists for several hours.

The following prescription medications contain morphine:

Astramorph PF®

Duramorph®

MSIR®

MS Contin Tablets®

Roxanol®
25

The following prescription medications contain codeine:

Actifed with Codeine Cough Syrup®

Codimal PH® Syrup

Dimetane-DC Cough Syrup®

Emprin with Codeine®

Fiorinal with Codeine®

Phenaphen with Codeine®

Robitussin A-C®

Triaminic Expectorant with Codeine®

Tylenol with Codeine(#1, 2, 3, or 4)®

Tussar-2®

Note: The above lists are only a representative sample of the prescription medications 

that contain codeine or morphine. 

The following nonprescription products contain opium (i.e., morphine):

Amogel PG®

Diabismul®

Donnagel-PG®

Infantol Pink®

Kaodene with Paregoric®

Quiagel PG®

Paregoric

The following nonprescription product contains codeine:

Kaodene with Codeine®

Note: Each listed nonprescription product is used as an antidiarrheal. They are 

generally availably over-the-counter; however, nonprescription sale is prohibited in 

some states. Paregoric alone is a Schedule III prescription drug, but in combination with 

other substances is a Schedule V over-the-counter product. 

The following substance metabolizes to morphine:

Heroin

2. Metabolism and Excretion

Heroin (diacetylmorphine) is rapidly deacetylated to 6-acetylmorphine (6-AM; also called 

6-monoacetylmorphine, 6-MAM), and, therefore, heroin itself is rarely ever detected in 

the urine. Heroin's characteristic metabolite, 6-AM, is rapidly deacetylated to morphine, 

and will likely not be detected in most urine specimens of heroin users. Since codeine is 

a naturally occurring alkaloid in the same opium poppy juice that is the source of 

morphine used as the starting material for heroin synthesis, codeine may be found in 

the urine of heroin users. 

Morphine is rapidly absorbed and excreted as unchanged morphine and as conjugated 
26

glucuronides (i.e., morphine-3-glucuronide, morphine-6-glucuronide). The primary 

metabolite is morphine-3-glucuronide. Morphine and its metabolites can be detected in 

urine up to about 4 days after its use.

Codeine (methylmorphine) is also rapidly absorbed and is excreted as unchanged 

codeine, morphine, and glucuronide conjugates.

Since the body metabolizes codeine to morphine, both substances (i.e., codeine and 

morphine) may occur in the urine following the use of codeine. Recently ingested 

codeine explains the presence of both drugs in the urine specimen (i.e., parent drug 

codeine and morphine metabolite). After the ingestion of a legitimate medical 

preparation containing codeine, there comes a time when parent codeine has been 

completely excreted or metabolized to morphine, so that morphine only is detected in 

the urine.

Ingestion of morphine in any form will never account for the presence of codeine in the 

urine (codeine is not a metabolite of morphine).

Note: There are a number of synthetic or semisynthetic analgesics available including, 

but not limited to, alphaprodine (Nisentil®), hydromorphone (Dilaudid®), oxymorphone 

(Numorphan®), hydrocodone (Hycodan®), dihydrocodeine (Paracodin®), oxycodone 

(Percodan®), propoxyphene (Darvon®), methadone (Dolophine®), meperidine 

(Demerol®), fentanyl (Sublimaze®), pentazocine (Talwin®), and buprenorphine 

(Buprenex®). These drugs do not metabolize to either codeine, morphine, or 6-

acetylmorphine. When a donor presents a prescription for a narcotic analgesic, the 

MRO must verify that it does not contain codeine or morphine and, therefore, cannot 

metabolize to codeine, morphine, or 6-acetylmorphine. 

3. Interpreting Laboratory Result

The opiate drug class poses some unique challenges with regard to interpreting a 

positive test result. A positive for codeine or morphine may be a result of a donor having 

taken a prescription medication that contains codeine or morphine or a donor 

consuming normal dietary amounts of poppy seeds. In addition, for the opiate drug 

class, there is a requirement to document clinical evidence of illegal use.

Note: Before an MRO verifies a confirmed positive result for opiates, he or she shall 

determine that there is clinical evidence - in addition to the urine test - of illegal use of 

any opium, opiate, or opium derivative. The main issue is the MRO must substantiate 

that there is "clinical evidence of illegal use" of an opiate substance before a positive 

result reported by a laboratory can be verified as a "Positive." Clinical evidence of illegal 

use may include, but is not limited to: a donor admits taking a prescription medication 

containing codeine or morphine that was prescribed to another individual; recent needle 

marks; or behavioral and psychological signs of acute opiate intoxication or withdrawal. 

If "clinical evidence of illegal use" is not present, the MRO must verify the "Positive" 

result reported by the laboratory as a "Negative" result to the employer. 
27

Note: The 6-acetylmorphine metabolite comes only from heroin; therefore, its presence 

confirms the illegal use of heroin. When the presence of 6-AM is confirmed, there is no 

requirement for clinical evidence.

Note: For a positive morphine or codeine test result, an MRO may have a blanket 

written request on file at the laboratory to routinely receive the quantitative values 

associated with a positive codeine and morphine result. The MRO also may request 

quantitative information on the presence of codeine below the cutoff for specimens

which have been reported positive for morphine only. This information may be helpful to 

the MRO in assessing the medical explanation provided by the donor.

Note: Quantitative test results may not

a. Admits taking morphine or codeine 

be requested by the MRO from the testing 

laboratory on a routine basis for the other drug categories, but may be requested on a 

case-by-case basis. 

The donor provides the following response:

illegally

b. Claims to have taken a prescription medication.

or using heroin. The MRO verifies the 

result as a "Positive" for the drug reported by the laboratory.

The MRO requests the donor to provide a copy of the prescription or the medication 

with the appropriately labeled prescription.

Even if no valid medical explanation is provided by the donor, the MRO must verify and 

report the result as "Negative" unless there is clinical evidence of the abuse or illegal 

use of opiate drugs.

Note: The presence of 6-acetylmorphine (6-AM) confirms the illegal use of heroin and, 

therefore, it is not necessary to verify clinical evidence of illegal use. 

Note: The MRO must verify as "Negative" any codeine or morphine test result for which 

the donor has taken a legally prescribed codeine or morphine medication.

Note: Occasionally, a donor will reveal information regarding the use of a narcotic 

analgesic (that does not contain codeine or morphine) believing that this medication 

was the reason for the positive codeine or morphine. Assuming that it was a legally 

prescribed medication, this confidential medical information cannot be provided to the 

employer and is not an explanation for the positive codeine or morphine. Since the use 

of a narcotic analgesic may have a possible effect on the ability of the donor to perform 

a specific task (such as, driving a vehicle), it may be appropriate to discuss the use of 

the medication with the prescribing physician. See Section G in Chapter 4 regarding the 

reporting of this information.

c. Claims to have eaten foods that contain poppy seeds.
28

One reason for the requirement for clinical evidence of abuse or illegal use in opiate 

testing is that eating a normal dietary amount of poppy seeds can cause a urine 

specimen to test positive for morphine and codeine (i.e., they contain trace amounts of 

morphine with or without codeine). In many instances, a donor will not know that poppy 

seeds can cause a positive test or that he or she had eaten poppy seeds at the time the 

urine was collected. The concentration of morphine can be substantial, with usually very 

low concentrations or no detectable codeine. Unless clinical evidence of abuse or illegal 

use of opiates is verified, the MRO must verify and report the result as a "Negative."

E. Phencyclidine

1. Background

Phencyclidine (PCP), an arylcyclohexylamine, was first synthesized in the 1950's as a 

general anesthetic. Street names include Angel Dust, Crystal, Killer Weed, Supergrass, 

and Rocket Fuel. PCP's synthesis is relatively simple for clandestine laboratories. 

Phencyclidine's use as a human anesthetic was discontinued because it produced 

psychotic reactions ("emergence delirium"), and its more prolonged use as a veterinary 

tranquilizing agent also has stopped. PCP is currently a DEA Schedule II controlled 

substance, has no current therapeutic role, and all uses are illegal. The preferred route 

of ingestion is smoking, but it may be eaten, snorted, or injected intravenously.

PCP is best classified as a hallucinogen and has a variety of effects on the central 

nervous system. Intoxication begins several minutes after ingestion and usually lasts 

eight hours or more. PCP is well known for producing unpredictable side effects, such 

as psychosis or fits of agitation and excitability. PCP clearly has drastic effects on 

performance. Clinical cases have documented the severe debilitating physical and 

psychological effects of PCP abuse and the extremely unpredictable behavior caused 

by the drug.

Intoxication may result in persistent horizontal nystagmus, blurred vision, diminished 

sensation, ataxia, hyperreflexia, clonus, tremor, muscular rigidity, muteness, confusion, 

anxious amnesia, distortion of body image, depersonalization, thought disorder, auditory 

hallucinations, and variable motor depression or stimulation, which may include 

aggressive or bizarre behavior. 

2. Metabolism and Excretion

PCP is well absorbed by any route and is excreted as unchanged PCP and as 

conjugates of hydroxylated PCP. About 10 percent of the PCP dose is excreted in the 

urine as the parent compound. PCP is a weak base which concentrates in acidic 

solutions in the body. Because of gastric acidity, PCP repeatedly reenters the stomach 

from plasma, later returning into plasma from the basic medium of the intestine.

Generally, PCP is considered detectable in urine for several days to several weeks 
29

depending on the frequency of use. 

3. Interpreting Laboratory Result

The donor provides the following response:

a. Admits or denies using PCP. The MRO verifies the result as "Positive" for PCP.

b. Claims to have taken a prescription or over-the-counter medication. The MRO 

verifies the result as "Positive" for PCP. There are no prescription or over-thecounter medications that contain PCP, legal medical uses of PCP, or any other 

substances that can be misidentified as PCP using gas chromatography/mass 

spectrometry.

Chapter 5. Documentation and Recordkeeping

A. Recordkeeping

Accurate recordkeeping is essential in documenting all aspects of the MRO review 

process. All communications, written or oral (including, but not limited to, those with 

donors, employer representatives, laboratory personnel, and collectors) must be 

appropriately documented. 

Although the Guidelines do not specify the length of time that MROs must retain these 

records, it is recommended that they be maintained for a minimum of two years from the 

date of collection, or as otherwise provided by law or contract with the employer.

Note: This two-year recommendation agrees with the requirement that each laboratory 

must retain records associated with the testing of a specimen for a minimum of 2 years.

No regulatory requirements exist requiring MROs to use a specific procedure to review 

drug tests; however, using a standard procedure is likely to ensure that each MRO 

review is complete and thorough. The use of a simple checklist will ensure that certain 

activities are always documented. 

Documentation must normally include such things as copies of prescriptions or labels 

on prescription bottles, or notes that a prescription was verified at a pharmacy or by the 

treating physician. Any letters or notes received from an employee, relative, or physician 

providing treatment must be retained in the file. 

Finally, MRO records must be separated from other medical and personnel records kept 

on an individual. For example, some physicians may also serve as a primary care 

provider and retain medical records related to that function. 

B. Confidentiality

The Guidelines require the MRO to report the final result of the drug test to an employer 
30

in a manner designed to ensure the confidentiality of the information. The MRO also has 

a responsibility to maintain the confidentiality of the information received during the 

review process, including information related to the donor's medical condition, 

medications, medical diagnosis, and medical history. This role is particularly important 

with respect to confirmed "Positive" drug test results, and especially for those that may 

be verified by the MRO as "Negative" due to an alternative legitimate medical 

explanation. 

Despite this general requirement to maintain the confidentiality of medical information, 

there are certain circumstances in which the MRO may provide such information to 

other parties. In these instances, the MRO must inform the donor, prior to the medical 

interview, that disclosure of information learned as part of the medical review process 

may occur if, in the judgment of the MRO, the information suggests there is a significant 

safety hazard associated with the information or there is a medical disqualification of the 

donor under an applicable regulation.

Note: Such information may also be released under other circumstances specified by 

Federal agency regulations.

Even when the MRO releases otherwise confidential information due to such concerns, 

the MRO must attempt to release as little specific information as possible and release 

such information only to parties with a clear need-to-know. Such parties include 

physicians responsible for medical certification of the donor, Federal agency officials as 

required by regulation, or designated employer representatives.

Diagnoses or other specific details of medical information do not need to be provided to 

non-medical personnel. For example, employer representatives may only need to be 

informed that a safety hazard may exist and that the MRO needs to provide specific 

information to the physician responsible for making medical qualification decisions 

regarding the donor. In general, unless required by regulation or law, the MRO must 

only discuss specific medical information with other physicians or qualified health 

professionals. 

A donor has the right, upon written request, to records relating to his or her drug test. In 

addition, information can be requested by a subpoena or court order. If an MRO has 

any concern regarding the release of information associated with drug testing results, 

the MRO may want to obtain a legal opinion.

Chapter 6. Additional MRO Responsibilities

A. Blind Quality Control Samples

Federal agencies and most employers regulated by DOT are required to have blind 

quality control samples submitted with the donor specimens. Blind quality control 
31

samples are helpful in determining if the entire testing process (i.e., from the collection 

of the specimen until a result is reported by the MRO) satisfies all requirements.

The blind quality control samples must be certified by immunoassay and GC/MS and 

have stability data which verifies their performance over time. The requirement to have 

certification data ensures that the blind quality control samples purchased from different 

sources are acceptable. 

Generally, the employer will request the collector to purchase the blind samples or may 

provide them to the collector. In either case, the collector must submit each quality 

control sample as if it were a donor specimen. This requires completing a CCF and 

properly labeling a specimen bottle. Since there is no donor associated with a quality 

control sample, the collector must generate a fictitious social security number or 

employee identification number and fictitious initials to be written on the specimen bottle 

label/seal. On Copy 2 of the CCF (MRO copy), the collector must indicate that the 

specimen is a "Quality Control Sample" where a donor would normally print his or her 

name. In addition, the collector or the employer, whichever purchased the blind 

samples, must forward that information to the MRO. This will allow the MRO to 

determine if the laboratory reported the correct result.

Note: An incorrect result reported by the laboratory does not automatically indicate that 

the laboratory made an analytical error. For example, there could have been a problem 

with the stability and/or concentration of the quality control sample or the collector did 

not properly submit the sample.

If the laboratory reports a result different from the one expected based on information 

provided by the manufacturer of the blind sample, the MRO must contact the laboratory 

to determine if there is an obvious reason why the laboratory did not report the expected 

result. If there is no obvious reason, the MRO may request the laboratory to retest the 

specimen or have an aliquot sent to another certified laboratory for confirmatory testing. 

If the retest result confirms the original result reported by the laboratory, it is most likely 

that an error occurred at the collection site or there was a problem with the quality 

control sample as purchased. If the retest result does not confirm the original result, the 

laboratory likely made an error.

Note: A false negative result (i.e., the laboratory reports a negative on a blind sample 

when a positive result was expected) is a concern, but must not be considered serious 

unless it occurs frequently and the MRO would not be expected to request the 

laboratory to retest the blind sample. However, a false positive (i.e., the laboratory 

reports a positive on a blind sample when a negative result is expected) is serious and 
32

must be investigated.

If the retest result has confirmed that a false positive was reported by the laboratory on 

a blind quality control sample, the MRO must contact the employer. The MRO must 

then contact the appropriate regulatory office who will conduct an investigation in an 

attempt to determine the exact cause of the false positive. When the specific cause is 

identified, appropriate corrective will be taken. The regulatory office will share the 

findings with the MRO.

B. Shy Bladder

Occasionally, a donor is unable to provide a specimen upon arrival at the collection site 

because he or she either urinated recently or has a "shy bladder." Generally, the term 

"shy bladder" refers to an individual who is unable to provide a sufficient specimen 

either upon demand or when someone is nearby during the attempted urination.

If it is believed that an individual has a "shy bladder," the employer must arrange to 

have the donor evaluated, as soon as practical after the attempted collection, by a 

licensed physician (e.g., the MRO, a physician acceptable to the employer, the 

employer’s occupational health physician) to determine whether the donor’s inability to 

provide a specimen is genuine or constitutes a refusal to provide a specimen.

The examining physician shall determine, in his or her reasonable medical judgment, 

that a medical condition has or, with a high degree of probability, could have precluded 

the employee from providing an adequate amount of urine (e.g., a urinary system 

dysfunction or a documented preexisting psychological disorder). An evaluation must 

include a review of any pertinent medical records and may include evaluative testing 

such as blood chemistries for kidney function or other physiologic factors likely to affect 

urine output.

Unsupported assertions of "situational anxiety" or dehydration are not considered valid 

reasons for a donor’s failure to provide an adequate amount of urine when sufficient 

time has elapsed and fluid volume has been ingested and shall be regarded as a refusal 

to take a test.

The examining physician shall provide to the MRO a brief written statement describing 

his or her conclusion and the basis for it. The written statement shall not include 

detailed information on the medical condition of the donor. Upon receipt of the written 

statement from the examining physician, the MRO shall report his or her conclusions to 

the employer in writing. 
33

C. Testing for an Additional Drug

HHS certified laboratories may only test regulated specimens for amphetamines, 

marijuana, cocaine, opiates, and phencyclidine. However, testing for an additional drug 

may occur for the following reasons:

1. There is reasonable suspicion/cause or a post accident incident for which testing 

for another drug listed in Schedule I or II of the Controlled Substances Act is 

justified; or 

2. A Federal agency was granted a waiver by the Secretary of HHS to routinely test 

its employees for another drug or drug class.

For any circumstance where testing for an additional drug is justified or authorized, the 

collector marks the "Other" box in Step 1 on the CCF and specifies the name of the 

drug(s) to be tested. There must also be a memorandum from the Federal agency 

attached to the CCF explaining why the specimen is being tested for the additional drug. 

Otherwise, the laboratory must not test for that additional drug.

Since the MRO will be reviewing a test result that is not a normal part of the Federal 

Workplace Drug Testing Program, the MRO may want to obtain a full documentation 

package from the laboratory to assess the forensic and scientific acceptability of the test 

result.