Russell J. Lewis

Roxane M. Ritter

Robert D. Johnson

Civil Aerospace Medical Institute

Federal Aviation Administration

Oklahoma City, OK 73125

Ryan W. Crump

University of Central Oklahoma

Edmond, OK 73034

December 2010

Final Report

Postmortem Concentrations of 

Tramadol and O-Desmethyltramadol 

in 11 Aviation Accident Fatalities

DOT/FAA/AM-10/19

Office of Aerospace Medicine

Washington, DC 20591

OK-11-0024-JAH

Federal Aviation

Administration
NOTICE

This document is disseminated under the sponsorship 

of the U.S. Department of Transportation in the interest 

of information exchange. The United States Government 

assumes no liability for the contents thereof.

___________

This publication and all Office of Aerospace Medicine 

technical reports are available in full-text from the Civil 

Aerospace Medical Institute’s publications Web site: 

www.faa.gov/library/reports/medical/oamtechreports
i

Technical Report Documentation Page 

1. Report No. 2. Government Accession No. 3. Recipient's Catalog No. 

DOT/FAA/AM-10/19 

4. Title and Subtitle 5. Report Date

Postmortem Concentrations of Tramadol and O-Desmethyltramadol in 11 

Aviation Accident Fatalities 

December 2010 

6. Performing Organization Code 

7. Author(s) 8. Performing Organization Report No. 

Lewis RJ,1 Ritter RM,1 Johnson RD,1 Crump RW2

9. Performing Organization Name and Address 10. Work Unit No. (TRAIS) 

1

Civil Aerospace Medical Institute 2University of Central Oklahoma 

P.O. Box 25082 Edmond, OK 73034 11. Contract or Grant No. 

Oklahoma City, OK 73125 

12. Sponsoring Agency Name and Address 13. Type of Report and Period Covered 

Office of Aerospace Medicine 

Federal Aviation Administration 

800 Independence Ave., S.W. 

Washington, DC 20591 14. Sponsoring Agency Code 

15. Supplemental Notes 

This work was accomplished under the approved task AM-B-10-TOX-204. 16. Abstract 

Tramadol is a centrally acting analgesic used to treat moderate-to-severe pain. Side effects of this medication 

include dizziness, confusion, drowsiness, seizures, and respiratory depression. Any of these side effects could 

negatively affect a pilot’s performance and become a factor in an aviation accident. Due to the severity of aviation 

accidents, blood samples are often not available, and frequently, only tissue specimens are available for analysis. 

Therefore, understanding the distribution of a drug throughout all fluids and tissues of the body is important 

when trying to interpret drug impairment and/or intoxication. Our laboratory has determined the distribution of 

tramadol and its main active metabolite, O-desmethyltramadol, in various postmortem tissues and fluids obtained 

from 11 fatal aviation accident cases. Whole blood tramadol concentrations obtained from these 11 cases ranged 

from 81-2720 ng/mL. When available, 10 specimen types were analyzed for each case, including blood, urine, 

vitreous humor, liver, lung, kidney, spleen, muscle, heart, and brain. Distribution, expressed as specimen/blood 

ratio, for tramadol was 69 ± 74 in urine, 2.58 ± 3.26 in vitreous humor, 4.90 ± 3.32 in liver, 3.43 ± 2.31 in lung, 

3.05 ± 1.49 in kidney, 5.15 ± 2.66 in spleen, 1.18 ± 0.85 in muscle, 2.33 ± 1.21 in brain, and 1.89 ± 1.01 in 

heart. Distribution coefficients obtained had coefficient of variations (CV) ranging from 49-126%. With such 

large CV’s, the distribution coefficients have little use in predicting blood concentrations from the analysis of a 

tissue specimen. This study indicates that tramadol concentrations undergo significant postmortem changes. 

17. Key Words 18. Distribution Statement 

Forensic Toxicology, Tramadol, Distribution, GC/MS, 

Forensic Toxicology 

Document is available to the public through the 

Defense Technical Information Center, Ft. 

Belvoir, VA 22060; and the National Technical 

Information Service, Springfield, VA 22161 

19. Security Classif. (of this report) 20. Security Classif. (of this page) 21. No. of Pages 22. Price 

Unclassified Unclassified 10

Form DOT F 1700.7 (8-72) Reproduction of completed page authorized 

iii

Contents

Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

 Chemicals and Reagents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

 Sample Selection and Storage. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Gas Chromatographic/Mass Spectroscopic Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

 Calibrator and Control Preparation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

 Sample Preparation and Extraction Procedure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Results and Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

 Analysis of Tramadol. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

1

Postmortem Concentrations of Tramadol and O-Desmethyltramadol

in 11 Aviation Accident Fatalities

Introduction

The Federal Aviation Administration’s (FAA’s) Civil

AerospaceMedicalInstitute(CAMI)isresponsibleunder

Department of Transportation Orders 8020.11B and

1100.2C to “conducttoxicological analysis on specimens

from ... aircraft accident fatalities” and “investigate ...

general aviation and air carrier accidents and search for

biomedical and clinical causes of the accidents, including evidence of ... chemical (use).” Therefore, following

an aviation accident, samples are collected at autopsy

and sent to CAMI’s Bioaeronautical Sciences Research

Laboratory, where toxicological analysis is conducted

on various postmortem fluids and tissues. Occasionally,

during a toxicological evaluation, potentially impairing

compounds are detected in postmortem specimens from

aviation accident victims. 

Tramadol (2-[(dimethylamino) methyl]-1-(3-methoxyphenyl)cyclohexanol), sold under the brand name

Ultram, is a centrally acting analgesic prescribed for the

treatmentofmoderatetoseverepain.

1

 The Foodand Drug

Administration approved tramadol in 1995 for legal use

in the United States. Impairing sideeffectsfromthe usage

oftramadolincludedizziness, confusion,light-headedness

or fainting spells, drowsiness, seizures and respiratory

depression.

2-4 Tramadol undergoesextensive metabolism

by O- and N-demethylation (Figure 1). Dueto its higher

affinity for the μ-opioid receptor, O-desmethyltramadol

has 2-4 times the efficacy of tramadol, whereas, Ndesmethyltramadol has little therapeutic effect.

4

Postmortem concentrations of tramadol following drug overdose has been reported in the scientific

literature.

1,5-11 However, little information concerning

postmortem concentrations and distribution of tramadol at therapeutic levels has been reported.

12 Since

scientific information concerning the distribution of

tramadol, when present at therapeutic concentrations,

is very limited, our laboratory set out to determine its

distribution in various postmortem tissues and fluids. 

A search of our internal laboratory database identified

11 aviation fatalities where tramadol was detected in

blood, which also had a full complement of biological

tissues andfluids availableforfurther analysis. Thespecimen types included urine, vitreous humor, lung, liver,

HO

N

H3C

H3C

O

CH3

HO

N

H3C

H3C

OH

HO

NH

H3C

O

CH3

Tramadol O-Desmethyltramadol

N-Desmethyltramadol

 Figure 1. Chemical structures of tramadol and its metabolites.
2 

kidney, spleen, muscle, heart, and brain. This report

presents the quantitation and distribution of tramadol

in postmortem specimens.

Materials and Methods

Chemicals and Reagents

Tramadol and O-desmethyltramadol were purchased

from Cerilliant (Cerilliant Corp., Round Rock, TX) at

a concentration of 1.00 mg/mL in methanol. C13D3

-

tramadolwaspurchasedfrom Cerilliant at a concentration

of 100 μg/mL in methanol. Methanol, acetic acid, potassium phosphate dibasic, sodium fluoride, ammonium

hydroxide, and ethyl acetate were purchased from Fisher

Scientific (Fisher Scientific, Inc.; Pittsburgh, PA) in the

highest possible purity. Double deionizedwater(DDW),

was obtained using an ELGA, PURELAB Ultra water

system (ELGA, Inc.; Lowell, MA).

Sample Selection and Storage

A searchofthe CAMItoxicologydatabase(ToxFLOTM,

DiscoverSoft Development, LLC; Oklahoma City, OK)

identified 11 tramadol-positive fatalities from separate

civil aviation accidents that occurred during a period of

3 years (2006-2008). Each of these cases had a majority

of the desired biological tissues and fluids available for

further analysis(blood, urine, vitreous humor, lung, liver,

kidney, spleen, muscle, heart, and brain). In each case,

blood was stored at -20°C in tubes containing 1.00%

(w/v)sodiumfluoride/potassiumoxalatepriortoanalysis. 

All other specimen types were stored without preservation at -20°C until analysis. Whole-blood tramadol

concentrations determined in this study agreed wellwith

those previously determined by our laboratory. In fact,

tramadol concentrations found were within 10% of the

value originally determined, verifying that no deterioration had occurred under these storage conditions.

Gas Chromatographic/Mass Spectroscopic 

Conditions

All analyses were performed using a bench top gas

chromatograph-mass spectrometer (GC/MS) consisting

of a Agilent 6890 seriesGC connected to an Agilent 5973

quadrupole MS (Agilent; Palo Alto, CA). The GC/MS 

was operated with a transfer line temperature of 280°C 

and a source temperature of 250°C. Chromatographic

separation was achieved using a FactorFour®, crosslinked, 100% methyl siloxane capillary column (12m

x 0.2mm-i.d., 0.33-μm film thickness) obtained from

Varian (Varian, Inc.; Santa Clara, CA). The carrier gas

utilizedwas helium,with a flowrate of 1.0 mL/min. One

μL was injected into the GC/MS using an Agilent 7683

autosampler. The GC was equipped with a split/splitless

injection port operated at 250°C in the splitless mode

with the purge time of 0.50 min. The oven temperature

profile was 100°C to 290° at 30°C/min, with a final

hold time of 0.67 min for a total run time of 7.00 min.

Neat standards of each compound were analyzed

individually using the full-scan mode of the GC/MS to

select appropriate quantitation and qualifier ions. The

MS was run in selected ion monitor (SIM) mode with

a dwell time of 20 ms. Ions monitored were m/z 263.2,

218.2 and 135.1 for tramadol, m/z 249.2, 218.2, and

135.1 for O-desmethyltramadol, and m/z 267.2, 222.2

and 139.1 for C13D3

-tramadol. 

Acceptability criteria employed for analyte identification and quantitation were as follows: (1) ion ratios for

a given analyte, measured as the peak area of a qualifier

ion divided by the peak area of the quantitation ion,were

required to be within ± 20% of the average of the ion

ratios for each respective calibrator used to construct the

calibration curveforthat analyte;(2)each ionmonitored

was required to have a minimum signal-to-noise ratio

(S/N) of 10; and (3) the analyte was required to have a

retention time within ± 2.00% of the average retention

time for each respective calibrator used to construct the

calibration curve for that analyte. Analytes not meeting

these criteria were reported as either negative or inconclusive.

Calibrator and Control Preparation

Calibration curves for tramadol and O-desmethyltramadol were prepared by serial dilution, utilizing bovine

whole blood as the diluent. Calibrators were prepared

from one set of original stock standard solutions, while

controls were prepared in a similar manner as calibrators

– but from a second set of unique stock solutions. The

calibration curve was prepared at concentrations ranging

from 6.25 to 1600 ng/mL. A minimum of six calibrators

were used to construct each calibration curve. Controls

were prepared at concentrations of 80, 160, 320, and 640

ng/mL and extracted with each batch of unknowns to

verify the accuracy of the established calibration curve. 

Controls were made fresh daily due to breakdown of

O-desmethyltramadol. An aqueous internal standard

solution, C13D3

-tramadol, was prepared at a final concentration of 400 ng/mL.

Sample Preparation and Extraction Procedure

All tissue samples were homogenized using an Omni

post-mounted homogenizer (Omni International.; Kennesaw, GA). Tissue samples were diluted with a 1.00%

NaF solution in a 1:2 (tissue:1% NaF solution) dilution

prior to being homogenized. Three mL aliquots of each
3

calibrator, control, postmortemfluid, and 3.00 g aliquots

ofeachtissuehomogenateweretransferredintoindividual

16 x 150-mm screw-top tubes. A 1 mL aliquot of the

stock internal standard (400 ng) solution was added to

each sample. Six mL of 0.10 M phosphate buffer (pH 

6.00) was added to each tube and mixed vigorously. The

specimens were then centrifuged at 820 x g for 45 min. 

Following centrifugation, the extracts were transferred

to Bond Elute Certify® solid-phase extraction (SPE)

columns (Varian, Inc.), which had been pre-conditioned

with 2 mL methanol followed by 2 mL of 0.10 M phosphate buffer (pH 6.00). Care was taken to prevent the

columns from drying prior to sample addition. Column

flow rates of 1-2 mL/min were maintained in each SPE 

step using a Varian Cerex® 24-port, positive-pressure

extraction manifold with a nitrogen pressure of 3 psi. 

After each sample passed through its respective column,

all SPE columns were washed with 1 mL of 1.0 M acetic

acid and dried for 5 min with 25 psi of nitrogen. Once

dry, the columns were again washed by adding 6 mL of

methanol to each. The columns were again dried with

nitrogen at 25 psi for 5 min. The analytes of interest were

eluted from the columns with 3 mL of 2% ammonium

hydroxide in ethyl acetate and evaporated to dryness in

a TurboVap concentrationworkstation (Caliper Life Sciences; Hopkinton, MA) set at 40°C under a stream of

dry nitrogen. Once dried, the residue was reconstituted

in 50 μL of ethyl acetate and transferred to GC/MS 

autosampler vials for analysis. 

Results and Discussion

Analysis of Tramadol

The described procedure, utilizing SPE and GC/MS,

proved to be a rapid and sensitive method forthe analysis

of tramadol and O-desmethyltramadol. Analyte peaks

were completely resolved, andeachprovidedquantitation

ions with unique m/z, so no interference was observed. 

Deuterated tramadol was used as internal standards for

this study. This eliminated any concerns over possible

matrix effects and allowed for accurate quantitation in

specimen types other than whole blood while utilizing a

whole blood calibration curve. No analytesuffered interferencefromendogenous/exogenousmatrix components.

Thelineardynamic range(LDR) andlimitofquantitation(LOQ)forbothtramadol andO-desmethyltramadol

weredetermined,usingbovinewholebloodasthematrix. 

The LDR for each analyte was determined to be 6.25-

1600 ng/mL. The calibration curves for tramadol and

O-desmethyltramadol had correlation coefficients of

0.998 and 0.997, respectively. The LOQ, defined as the

lowest detectable analyte concentration that meets all

identification criteria discussed in the method section,

in addition to being within 20% of its target concentration, for both tramadol and O-desmethyltramadol was

determined to be 6.25 ng/mL. The LOD, defined as the

lowest detectable analyte concentration that meets all

identification criteria discussed in the Method section,

was determined to be 1.56 ng/mL for tramadol and 3.13

ng/mL for O-desmethyltramadol.

Carryover was not found to be a problem on the GC/

MS;however,itwasinitially investigatedandsubsequently

monitored by the use of ethyl acetate blank injections. 

The injection of an ethyl acetate blank following the

1600 ng/mL calibrator showed no carryover contamination. Subsequently, two ethyl acetate blankswere utilized

between each postmortem specimen throughout the

sample sequence to verify that no carryover from sample

to sample had occurred.

Postmortem Concentrations of Tramadol and ODesmethyltramadol

Tramadol blood concentrations found in these 11

postmortem cases ranged from 0.081 to 2.72 μg/mL. 

Therapeutic blood concentrations range from 0.150 to

0.800 mg/mL.5

 Toxic levels of tramadol have been reported at concentrations as low as 1.40 μg/mL.13 Lethal

levels of tramadol have been reported at concentrations

as low as 2.00 μg/mL.13 Blood concentrations observed

in this study ranged from slightly below therapeutic

to toxic levels. However, a previous study found that

tramadol concentrations in impaired drivers overlapped

with concentrations found in tramadol overdoses.

14 Additionally, thesitefrom which the blood was collected at

autopsy is unknown foreach of these cases. Thus, dueto

postmortem redistribution, these blood concentrations

may not be representative of the levels observed prior to

death. The concentration of these compounds in each

postmortem specimen analyzed from these 11 cases can

be seen in Tables 1 and 2.

Thefollowing mean concentrations (μg/mL, μg/g) of

tramadolwerefound:0.771inblood(0.081-2.72,n=11),

29.72inurine(0.461-152,n=10),1.01invitreoushumor

(0.092-4.45,n=6),2.55inliver(0.303-7.74,n=11),2.23

in lung (0.075-6.58, n=10) 1.45 in kidney (0.221-3.63,

n=11),2.29inspleen(0.286-6.69,n=11),0.583inmuscle

(0.077-2.15,n=11),1.10inbrain(0.117-3.08,n=11), and

0.088 in heart (0.084-2.48, n=11). The following mean

concentrations (μg/mL, μg/g) of O-desmethyltramadol

were found: 0.043 in blood (0.017-0.085, n=5), 4.78

in urine (0.670-9.65, n=9), 0.479 in liver (0.142-1.23,

n=7), 0.358 in lung (0.032-1.26, n=7), 0.279 in kidney

(0.055-0.914, n=8), 0.298 in spleen (0.062-0.871, n=8),

0.136 in muscle (0.071-0.174, n=3), 0.151 in brain
4 

Table 1. Tramadol concentrations obtained from 11 pilot fatalities.*

Case Blood Urine VH Liver Lung Kidney Spleen Muscle Brain Heart

1 0.151 9.59 0.381 1.46 1.11 0.690 1.07 0.259 0.462 0.397 

2 0.636 77.17 — 3.17 4.54 2.00 3.96 0.664 1.39 1.80 

3 0.606 152.03 1.04 7.74 — 3.41 6.69 2.15 2.87 1.67 

4 2.72 15.87 — 4.80 6.58 3.63 3.52 1.33 3.08 2.48 

5 0.222 7.36 — 1.36 0.950 1.17 1.44 0.306 0.806 0.697 

6 2.50 23.51 0.084 6.61 4.34 2.60 4.50 0.927 1.85 1.31 

7 0.260 6.90 — 0.880 3.37 0.851 1.25 0.244 0.420 0.502 

8 0.462 3.40 4.45 1.13 0.798 0.942 1.493 0.284 0.597 0.398 

9 0.093 1.05 0.038 0.157 0.075 0.146 0.286 0.054 0.117 0.084 

10 0.091 0.461 — 0.429 0.353 0.273 0.602 0.120 0.313 0.301 

11 0.081 — 0.092 0.303 0.115 0.221 0.405 0.077 0.206 0.086 

* All concentrations shown in units of g/mL or g/g

— Specimen type not available for analysis 

Table 2. O-Desmethyltramadol concentrations obtained from 11 pilot fatalities.*

Case Blood Urine VH Liver Lung Kidney Spleen Muscle Brain Heart

1 0.017 1.730 neg 0.142 0.063 0.090 0.062 neg 0.045 0.039 

2 neg 9.65 — 1.23 1.26 0.914 0.871 0.174 0.268 0.347 

3 0.031 9.53 neg 0.492 - 0.183 0.275 0.071 0.157 neg 

4 neg 0.744 — neg 0.130 0.102 neg neg 0.053 neg 

5 0.056 7.16 — 0.228 0.093 0.189 0.191 neg 0.194 0.146 

6 neg 5.45 neg 0.932 0.540 0.601 0.619 0.164 0.300 neg 

7 neg 6.23 — 0.149 0.389 neg 0.148 neg neg neg 

8 0.085 1.87 neg 0.178 neg neg neg neg neg neg 

9 neg neg neg neg neg neg neg neg neg neg 

10 neg 0.670 — neg neg 0.094 0.146 neg neg neg 

11 0.028 — neg neg 0.032 0.055 0.070 neg 0.038 neg 

* All concentrations shown in units of g/mL or g/g

— Specimen type not available for analysis 
5

(0.038-0.300, n=7), and 0.177 in heart (0.039-0.347,

n=3), and each vitreous humor specimen was negative. 

Thedistributioncoefficientsfortramadol,expressedas

specimenconcentration/bloodconcentration,werefound

to be: 69 ± 74 urine, 2.58 ± 3.26 vitreous humor, 4.90

± 3.32 liver, 3.43 ± 2.31 lung, 3.05 ± 1.49 kidney, 5.15

± 2.66 spleen, 1.18 ± 0.85 muscle, 2.33 ± 1.21 brain,

and 1.89 ± 1.01 heart. The distribution coefficients for

O-desmethyltramadol,expressed asspecimen concentration/blood concentration, were 140 ± 121 urine, 7.60 ±

6.10 liver, 6.51 ± 1.36 lung, 4.13 ± 1.80 kidney, 4.61 ±

2.89 spleen, 3.13 ± 1.55 brain, and 2.45 ± 0.22 heart. 

NodistributioncoefficientforO-desmethyltramadolwas

determined in either vitreous humor or muscle due to

an insufficient number of replicates for these specimen

types. A detailed listing of the distribution coeficients are

shown in Tables 3 and 4.

Tramadol distribution coefficients obtained in this

study had coefficient of variation (CV) values that

ranged between 49 and 126%. Thesametissuesamples

produced CV values for O-desmethyltramadol that

ranged from 9 to 80%. The large CV values associated with the distribution coefficients obtained suggest a high degree of inter-individual variation in the

distribution of these compounds. This inconsistency

could result from numerous factors, sush as differing

blood collection sites at autopsy, postmortem interval,

postmortem redistribution, and contamination. The

blood collection site and postmorteminterval forthese

cases are unknown. However, in most of our cases in

which the collection site is noted, the blood typically

originates from the chest cavity. Alkaline compounds

readily undergo postmortem redistribution in the

interval between death and specimen collection. This

redistribution could account for some of the larger

CV values obtained. Additionally, with a relatively

small volume of distribution (3 L/kg),13 one would

expect tramadol concentrations obtained from tissue

specimens to besimilar to thosefound in whole blood. 

This was not consistent with our findings, which suggests that postmortem changes in drug concentrations

had occurred.

Drug concentrations determined from a blood specimen can aid in determining impairment and/or cause

of death. However, due to the destructive nature of

aviation accidents, our laboratory receives blood in only

approximately70%ofthe casesexamined. If adistribution

coefficient with a CV < 20% is determined, it may be

possible,with caution,to use a tissue or fluid distribution

coefficient to roughly estimate a blood concentration in

cases where blood is not available for analysis. However,

theresultsobtainedfromourlimitednumberof casesshow

thattramadol blood concentrations cannot beestimated,

even crudely, from other tissue/fluid concentrations.

Table 3. Postmortem tissue distribution coefficients for Tramadol. 

Urine/

Blood

VH*/

Blood

Liver/

Blood

Lung/

Blood

Kidney/ 

Blood

Spleen/

Blood

Muscle/

Blood

Brain/

Blood

Heart/

Blood

n 10 6 11 10 11 11 11 11 11 

Mean 69.43 2.58 4.90 3.42 3.05 5.15 1.18 2.33 1.89 

s.d. 74.38 3.26 3.32 2.31 1.49 2.66 0.845 1.21 1.01 

CV 107.0 126.0 67.6 67.4 49.0 51.7 72.6 51.9 53.4 

* vitreous humor 

Table 4. Postmortem tissue distribution coefficients for O-Desmethyltramadol. 

Urine/

Blood

VH*/

Blood

Liver/

Blood

Lung/

Blood

Kidney/ 

Blood

Spleen/

Blood

Muscle/

Blood

Brain/

Blood

Heart/

Blood

n 4 — 4 3 4 4 — 4 2 

Mean 139.76 — 7.60 6.51 4.13 4.61 — 3.13 2.45 

s.d. 120.5 — 6.10 1.36 1.80 2.89 — 1.55 0.221 

CV 86.2 — 80.2 20.8 43.5 62.2 — 49.5 9.02 

* vitreous humor 
6 

Conclusion

Ourlaboratory identifiesnumeroustramadol-positive

cases each year. The undesirable side effects associated

with this medication is of concern in the aviation community. Withthisinmind, amethodfortheidentification

and quantitation of tramadol and its active metabolite,

O-desmethyltramadol, has been developed that is rapid,

reliable, and sensitive. By utilizing SPE, a clean extract

was achieved that required minimal time and solvent. A 

total of 103 tissue and fluid samples from 11 deceased

individuals were measured to determine tramadol and

O-demethyltramadol concentrations. Tramadol concentrations ranged from slightly below therapeutic to levels

that have been shown to be lethal in some cases. The

results obtained from these cases suggest that tramadol

is readily absorbed by all tissues and fluids in the body. 

The CV values obtained for the calculated distribution

coefficients were large; therefore, the tramadol distribution coefficients obtained should not be used to estimate

drug concentrations in whole blood from availabletissue

concentrations.

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