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Clinical Chemistry 52: 1539-1545, 2006. First published June 1, 2006; 10.1373/clinchem.2006.067983
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Right arrow Drug Monitoring and Toxicology
(Clinical Chemistry. 2006;52:1539-1545.)
© 2006 American Association for Clinical Chemistry, Inc.

Drug Monitoring and Toxicology

Opioid Disposition in Human Sweat after Controlled Oral Codeine Administration

Eugene W. Schwilke1, Allan J. Barnes1, Sherri L. Kacinko1, Edward J. Cone2, Eric T. Moolchan1 and Marilyn A. Huestis1,a

1 Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD.
2 Johns Hopkins School of Medicine Department of Psychiatry and Behavioral Sciences, Baltimore, MD.

aAddress correspondence to this author at: Chemistry and Drug Metabolism, Intramural Research Program, NIDA, NIH, 5500 Nathan Shock Dr., Baltimore, MD 21224. Fax 410-550-2971; e-mail mhuestis{at}intra.nida.nih.gov.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Background: Characterization of opioid excretion in sweat is important for accurate interpretation of sweat tests in drug treatment, criminal justice, and workplace drug testing programs.

Methods: Participants (n = 20) received placebo, 3 low (60 mg/70 kg) or 3 high (120 mg/70 kg) codeine sulfate doses (used as a model for opioid excretion) within 1 week. Codeine and metabolites in sweat were collected with PharmChek® Sweat Patches; hourly patches were applied for 1 to 15 h (n = 775) and weekly patches for 7 days (n = 118). Patches were analyzed by solid-phase extraction and gas chromatography–mass spectrometry for codeine, norcodeine, morphine, normorphine, and 6-acetylmorphine. Limits of quantification were 2.5 ng/patch (codeine and morphine) and 5 ng/patch (other analytes).

Results: Codeine was the only analyte identified in 12.6% of hourly patches and 83.3% of weekly sweat patches worn during dosing. Weekly patch concentrations (SD) were 38.6 (59.9) ng/patch [median (range), 15.9 (0–225.1) ng/patch] for low and 34.1 (32.7) ng/patch [24.0 (0–96.2) ng/patch] for high codeine doses. Codeine detected 1 week after dosing was 4.6 (5.3) ng/patch [median (range), 4.0 (0–17.1) ng/patch; n = 11] after low and 7.7 (7.1) ng/patch [6.9 (0–20.5) ng/patch; n = 10] after high doses. In total, 2.6% of hourly, 38.5% of low-dose, and 45.5% of high-dose weekly patches contained codeine at the proposed Substance Abuse and Mental Health Services Administration cutoff.

Conclusions: Codeine was the only analyte detected, at highly variable concentrations, up to 2 weeks after dosing. These results are consistent, considering the complex processes of codeine deposition in sweat. Sweat testing is a useful alternative technique for qualitative monitoring of opioid use.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Drug monitoring in treatment, criminal justice, and workplace programs provides objective data on drug exposure and verification of self-reported use. Since the invention of the PharmChek® sweat patch, sweat has been considered as an alternative matrix for drug testing. Sweat has a longer drug detection window than urine or plasma for most illicit drugs, its collection is noninvasive, and patches are relatively tamper resistant (1)(2).

The sweat patch is applied to the skin for several days to allow sufficient absorption of excreted drugs. Deposition of drugs into sweat depends on molecular mass, pKa, extent of protein binding, and lipophilicity (2). Nonionized basic drugs in blood diffuse into sweat and become ionized, leading to ion trapping in sweat because of its lower pH (3). Drugs in sweat on the skin’s surface may contribute to drug incorporation into hair (4). PharmChek sweat patches have been used to detect codeine (5)(6)(7), nicotine(8), cocaine (9)(10), heroin(11), cannabis (12), and methamphetamine(13)(14).

There are limited data on the excretion of opioids in sweat after controlled drug administration. Significant variability in codeine concentrations was observed in patches applied to various locations on the upper body (6). Codeine (2–127 ng/patch) was detected within 1 h and peaked within 24 h, and no metabolites were detected. Additionally, in a study showing good agreement between Drugwipe® (Securetec) and PharmChek sweat patch results (5), sweat patch codeine concentrations ranged from 3 to 124 ng/patch. In a different study, sweat patches worn for 2 days after codeine phosphate administration (15) had a mean codeine concentration <20 ng/patch. Another study examined excretion of heroin and metabolites after controlled administration of heroin (16). In sweat patches worn for 1 to 5 days, heroin (6.9–53.3 ng/patch) and 6-acetylmorphine [(6-AM); 1 5.7–38.5 ng/patch] were detected; no morphine was found.

After opioid self-administration, a small proportion of sweat patches from heroin abusers in a buprenorphine substitution program contained 67 to 4018 ng of codeine (7). Codeine concentrations of 13 to 900 ng/patch were noted in 206 of 925 patches collected from patients in a methadone maintenance program (17).

The Substance Abuse and Mental Health Services Administration (SAMHSA) recommends a confirmation cutoff of 25 ng/patch for codeine, morphine, and 6-AM in patches worn for 1 week (18). Whether patches applied weekly after last drug administration will be positive at the proposed SAMHSA cutoff remains unanswered. Data on the disposition of drugs into sweat after controlled administration provide a scientific basis for interpretation of sweat test results. However, the duration of opioid excretion in sweat is unknown but is critical for differentiating new drug use from residual drug excretion. Additionally, to date, only single-dose studies have been conducted, whereas multiple opioid self-administrations are characteristic of abuse of opioids. Finally, excretion data used as the scientific basis for the interpretation of sweat test results should be collected in a controlled environment to preclude self-administration of drugs. We addressed these issues, using codeine as a model for opioid excretion in sweat. During a 10-week study period, we administered 3 low (60 mg/70 kg) and 3 high (120 mg/70 kg) oral codeine doses to 20 human opiate users who resided continuously on a secure research unit. To characterize multiple aspects of codeine disposition in sweat, patches were worn for 4 different time intervals: (a) weekly washout patches worn before controlled dosing to monitor excretion of self-administered opiates; (b) hourly patches worn 1 to 15 h within the first 48 h after codeine administration; (c) patches worn for 1 week during dosing to investigate dose–concentration relationships and cumulative excretion of codeine over 1 week; and (d) patches applied weekly during the first and second weeks after the last codeine administration to determine the duration of codeine excretion in sweat. Duplicate patches were examined to determine reproducibility of codeine excretion in sweat.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
human participants
Twenty participants (14 male, 6 female; 70% African American, 20% Caucasian, 10% Hispanic; mean age, 34.1 years; range, 23–43 years) provided written informed consent for this within-subject, single-blind, placebo-controlled, Institutional Review Board-approved study. Participants underwent physical and psychologic examinations, and self-reported a history of opioid use. Participants resided on the closed clinical unit for 10 weeks and received 60 mg/70 kg (low), and 120 mg/70 kg (high) oral codeine sulfate, 3 times within weeks 4 and 8, respectively (Fig. 1A ), with at least 48 h between codeine doses. Placebo was administered 3 times during week 6.


Figure 1
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  		Figure 1. Codeine dosing timeline (A), and hourly sweat patch application schedule (B).

(A), codeine sulfate (60 mg/70 kg) was orally administered on Tuesday (T), Thursday (Th), and Monday (M) during week 4. Placebo was administered during week 6 and 120 mg/7 kg codeine sulfate was administered on Tuesday, Thursday, and Monday of week 8. (B), sweat patches were applied for 1, 2, 4, or 15 h after each low and high codeine administration, with at least 48 h between doses.

sweat collection
Duplicate patches, applied weekly to the abdomen or back, were worn during each week. Single hourly patches were worn for 1, 2, 4, or 15 h after each codeine administration according to the schedule described in Fig. 1BUp . After removal, patches were sealed in plastic bags and stored at –20 °C until analysis.

chemicals, reagents, and materials
Codeine sulfate was obtained from Roxane Laboratories and was encapsulated in polished capsules, provided by Amend Drug and Chemical. Methanol, acetonitrile, methylene chloride, 2-propanol, hydrochloric acid, ammonium hydroxide, and sodium acetate were obtained from J.T. Baker. Organic solvents were HPLC grade. N,O-bis(Trimethyl)trifluoro-acetamide with 1% trimethylchlorosilane (BSTFA +1% TMCS) and N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide with 1% tert-butyldimethylchlorosilane (MTBSTFA + 1% TBDMCS) were obtained from Pierce Chemical. Codeine, codeine-d3, norcodeine, morphine, morphine-d3, normorphine, 6-AM-d3, and 6-AM were purchased from Cerilliant. Clean Screen® ZSDAU020 extraction columns were obtained from United Chemical Technologies, and PharmChek sweat patches were provided by PharmChem Laboratories (Haltom City, TX).

patch preparation and analysis
Sweat patches were analyzed by a modified version of previously reported methodology (2). To calibrator patches we added 2.5, 5, 10, 25, 50, 100, 250, or 500 ng of codeine, norcodeine, morphine, normorphine, and 6-AM. To 4 control patches (3.75, 12.5, 125, and 375 ng), we added a solution prepared independently of the calibrator. Patches were placed in 15-mL fritted reservoirs with closed stopcocks, which in turn were placed over a vacuum manifold. To each reservoir we added 4 mL of 0.5 mol/L sodium acetate buffer (pH 4.0) and 100 µL of deuterium-labeled internal standard solution (1 mg/L). After 30 min, the solvent (4 mL) was collected and 2 additional washes (2 mL) were performed. Columns were conditioned with 1 mL of elution solvent (methylene chloride–isopropanol–ammonium hydroxide; 80:20:2 by volume), followed by water, methanol, and sodium acetate buffer. The samples were loaded, and the columns were washed with water, 0.2 mol/L hydrochloric acid, and methanol and dried under reduced pressure. Drugs were eluted by addition of 1 mL of elution solvent 5 times. To each tube we added 20 µL of MTBSTFA + 1% TBDMCS, after which the tubes were vortex-mixed, and the eluate was evaporated to dryness. Acetonitrile (0.5 mL) was added to each tube, the tubes were vortex-mixed, and the samples were again evaporated to dryness. The drugs were reconstituted in 20 µL of acetonitrile, vortex-mixed, and centrifuged. After centrifugation, 20 µL of MTBSTFA + 1% TBDMCS was added; the vials were then loosely capped and incubated for 15 min at 80 °C. After cooling, 20 µL BSTFA + 1% TMCS was added, and the vials were crimp-capped and incubated 45 min at 80 °C.

instrumentation
Samples (2 µL) were injected into an Agilent 6890 Gas Chromatograph/5973 Mass Selective Detector, equipped with an HP-1 [30 m x 0.32 mm (i.d.); 0.25-µm film thickness] column. The initial oven temperature was 70 °C, which held for 1 min; the temperature was then increased at 30 °C/min to 175 °C, increased 23 °C/min to 250 °C, increased 18 °C/min to 310 °C, and held for 3 min. Inlet temperature was 250 °C, pressure was 0.52 psi, and helium was the carrier gas. In the selected-ion monitoring mode, the ions monitored [target and qualifier(s) m/z] included codeine-d3 (m/z 374 and 237), codeine (m/z 371, 178, and 196), norcodeine (m/z 429, 254, and 292), morphine-d3 (m/z 417 and 474), morphine (m/z 414, 471, and 278), normorphine (m/z 472, 529, and 350), 6-AM-d3 (m/z 345 and 444), and 6-AM (m/z 342, 441, and 384). The limits of detection (LOD) and quantification (LOQ) were determined by serial dilution of a calibrator solution. The LOD was defined as the lowest concentration at which ions had a signal-to-noise ratio ≥3/1, ion ratios were within 20% of those of the calibrators, relative retention time was within 2%, and chromatography was acceptable. The LOQ criteria included all the LOD criteria and quantification had to be within 30% of the target. LOD and LOQ were 2.5 ng/patch for codeine, morphine, and 6-AM and 5.0 ng/patch for norcodeine and normorphine. Two separate calibration curves were constructed; a low curve from 2.5 to 50 ng/patch, and a high curve from 50 to 500 ng/patch. Drugs were quantified by linear regression with equal weighting. Quality-control samples were analyzed in each batch (see Table 1 in the Data Supplement that accompanies the online version of this article at http://www.clinchem.org/content/vol52/issue8/ ).

statistical analysis
Concentration means, medians, and ranges were calculated from all patches analyzed in the group, unless otherwise indicated. Statistical analyses were performed with SPSS, Ver. 13.0 for Windows, release 13.0.1. A paired t-test was used to compare sums of codeine concentrations in hourly patches with codeine concentrations in concurrently applied weekly patches. Spearman correlation analysis was used to determine the correlation between duplicate patch positivity rates. A two-tailed P value <0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
weekly washout patches
The 44 weekly washout patches from 13 participants, applied during the 3 weeks before codeine administration, were all negative for codeine, norcodeine, morphine, normorphine, and 6-AM, indicating that participants had not recently self-administered opiates. Corresponding plasma concentrations (19) also were negative for codeine and metabolites (LOQ, 2.5 µg/L) during washout weeks.

patches worn for 1 to 15 h
A total of 775 hourly patches from 20 participants were applied before, and worn for 1 to 15 h during the first 48 h after drug administration. Codeine, the only analyte detected in any patch, was found in 3 of 66 (4.5%) patches worn from 0 to 1 h after dosing (low and high doses combined). There was large intra- and intersubject variability in codeine concentrations in sweat during dosing weeks. Only 98 (12.6%) patches worn for 1 to 15 h (low and high doses combined) contained codeine at or above the LOQ (2.5 ng/patch), and 20 (2.6%) contained codeine at or above the proposed SAMHSA cutoff (25 ng/patch).

Hourly patches worn for longer periods within the first 24 h after dosing were more likely to contain codeine above the LOQ. Rates of positive hourly patches were 4.5% (n = 179), 13.3% (n = 75), 30.7% (n = 75), and 40% (n = 95) for patches worn 1, 2, 4, and 15 h, respectively. Detectability increased with wear duration, but codeine concentrations did not correlate with time worn or dose administered.

Codeine excretion occurred predominantly within the first 24 h after dosing (Fig. 2 ). Of the 15-h patches worn from hours 8 to 23 after low and high doses, 33.3% and 48.8%, respectively, had concentrations at or above the LOQ, compared with 2.5% (low), and 10.7% (high) of patches worn from hours 32 to 47 (Table 1 ). When we used the proposed SAMHSA guidelines (18), only 5.6% and 9.8% of 15-h patches, worn from hours 8 to 23 after low and high doses, respectively, were >25 ng/patch, whereas all 15-h patches worn from hours 32 to 47 were negative.


Figure 2
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  		Figure 2. Hourly sweat patch concentrations (SD) for 4 participants, worn during the first and second days after the first and second low (60 mg/70 kg) and high (120 mg/70 kg) doses.

Complete sets of hourly patches were not available after the third low and high codeine administrations. Patches were applied according to the schedule in Fig. 1BUp .


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  		Table 1. Codeine concentrations and comparison between the number of positive sweat patches at the method LOQ and SAMHSA cutoffs in all 15-h patches worn from hours 8 to 23 (including negative patches) after codeine administration.1

weekly patches worn during codeine administration
Weekly patches also were applied before the first of 3, and removed after the last of 3 codeine administrations (Table 2 ). Codeine was the only analyte detected in any patch, with no dose–concentration relationship.


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  		Table 2. Comparison between codeine concentrations in weekly sweat patches worn each week of the 10-week study.1

weekly patches worn after codeine administration
We examined the duration of codeine excretion in sweat, using duplicate weekly patches worn the first, second, and third weeks after the last of 3 low codeine administrations (weeks 5, 6, and 7), and the first and second weeks after the last of 3 high codeine administrations (weeks 9 and 10). Of the patches worn the first week after low and high doses, 63.6% and 70%, respectively, were positive for codeine above the LOQ, as were 2 of 8 patches worn the second week after the high doses. None were positive above the proposed SAMHSA cutoff.

analysis of duplicate patches
Codeine concentrations in duplicate weekly patches were compared to determine reproducibility of codeine sweat excretion (Table 2Up in the online Data Supplement). Patches were applied to the sides of the abdomen and worn the week of dosing or the first or second weeks after dosing. Twenty of 41 patch pairs were positive for codeine at the LOQ in at least one patch. Four pairs contained low concentrations of codeine (<12 ng/patch) in only one patch and were not included in statistical calculations. The mean (SD) difference in codeine concentration between positive duplicate patches was 5.9 (7.0) ng/patch [median (range), 3.0 (0.3–28.8) ng/patch]. Nine of 16 pairs (56%) were within 20%, 6 of 16 (38%) were within 40%, and 1 pair (6%) had a difference of >40%. There was a significant correlation between codeine concentrations in positive duplicate sweat patches (P <0.01).

cumulative excretion of codeine
We examined cumulative codeine excretion in sweat by comparing the sum of codeine concentrations in hourly patches with those in weekly patches (Table 3 ). Sixteen sets of positive weekly and hourly patches (low and high doses combined) were available for comparison. The sum of hourly patch concentrations was greater than weekly patch concentration in 11 sets, with a mean (SD) difference of 25 (19.8) ng/patch [median (range), 17.4 (0.3–57.5) ng/patch]. The mean hourly patch sum was 57.9 (60.4) ng/patch [41.0 (5.4–240.3) ng/patch], which was significantly higher than the mean corresponding weekly patch concentration [44.0 (55.5) ng/patch; median (range), 20.6 (1.7–225.1) ng/patch; P <0.05].


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  		Table 3. Cumulative excretion of codeine in sweat.1


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Metabolites of codeine were not detected in any sweat patch, which is partially explained by the physiochemical differences between plasma and sweat. Codeine, a lipophilic, basic compound, diffuses through membranes and becomes ionized in sweat at its lower pH (4–6), leading to accumulation and ion-trapping in this matrix. Norcodeine likely was not detected in sweat because it is present in much lower concentrations in blood and is less lipophilic than codeine. Morphine, a less lipophilic minor codeine metabolite, has a similar pKa of 8.1, but was not detected in any patch. The area under the curve for nonconjugated morphine in plasma was reported as 4.4% of the area under the curve for codeine after controlled codeine phosphate administration (19). Therefore, little free morphine is available for transfer into sweat.

Detection of codeine in the absence of its more polar metabolites also has been reported in other controlled codeine administration studies (5)(6); however, minor metabolites were detected in low concentrations in sweat under heat-stimulated conditions (2). Sudormed Fast Patches, a unique type of heat-activated sweat patch containing a metallic activation disc and food-grade sodium acetate, were applied to the torso and palms of the hands according to the same codeine dosing schedule as in the present study (2). Torso Fast Patches were positive for codeine and negative for metabolites; however, 8.3% of hand-held Fast Patches contained norcodeine at 11–26 ng/patch, and 7.1% contained trace quantities of morphine at ≤2 ng/patch. Differences in the skin anatomy and physiology of the torso and palms of the hands may have been responsible for observed differences in codeine and metabolite kinetics in sweat.

The time course of codeine excretion in sweat was evaluated with 1 to 15 h patches. Codeine detection depended on the duration of patch wear and when the patch was applied and removed relative to dosing. Codeine in hourly patches worn within the first 24 h after dosing increased from 4.5% in 1-h patches (n = 179) to 40% in 15-h patches (n = 95). Only 4.5% of 15-h patches were positive when worn 24 h after dosing (n = 67). Using a similar technique, Kintz et al. (6) observed peak codeine concentrations in the 12- to 24-h patch with lower concentrations from 72 to 98 h.

Participants in the present study received 3 codeine doses of 60 mg/70 kg within 1 week, followed 3 weeks later by 3 codeine doses of 120 mg/70 kg. Administration of multiple doses permitted evaluation of the dose–concentration relationship and more closely approximated drug usage patterns. To our knowledge, this is the first multiple-dose controlled opioid administration study that addresses dose–concentration relationships and stability of drug on the patch.

A possible mechanism of codeine deposition in sweat patches applied several days after last drug administration is release of the drug from adipose and cutaneous depots. Previous studies suggested that drugs may be present for long periods in the stratum corneum (20)(21) and in adipose tissue beneath the skin’s dermal layer (22). Hygienic washing with isopropanol did not completely remove externally applied cocaine, methamphetamine, and heroin, indicating that drugs are tightly bound in skin (1). In the present study, codeine remained detectable in plasma for only ~24 h (23). This demonstrates that codeine found in sweat patches applied up to 2 weeks after last codeine administration was the result of deposition from sources other than passive diffusion from blood.

Codeine concentrations in sweat patches were highly variable within and between participants. In 2 participants, all weekly patches applied during dosing were negative for codeine, whereas 3 hourly patches had concentrations <8.0 ng/patch. In a third participant, codeine was detected in weekly patches applied during dosing, the week after dosing, and in multiple hourly patches.

Data from this and other research suggest that the large intra- and intersubject variability is the result of multiple complex and dynamic metabolic processes. For example, the site of patch application on the body influences codeine concentrations in sweat (16)(24). Other sources of variability include differences in sweat output between individuals and potential loss or dynamic exchange of codeine between the patch and the skin (1)(24).

In this study, we also examined the reproducibility of codeine excretion in sweat. Duplicate patches were applied for 1 week during and 1 week after codeine administration. Four of 20 pairs contained codeine in only 1 patch. Overall, results of the present study indicated that codeine concentrations in duplicate sweat patches after controlled codeine administration were generally consistent at the method LOQ of 2.5 ng/patch and the proposed SAMHSA cutoff.

We examined the cumulative excretion of codeine in sweat by comparing codeine concentrations in weekly sweat patches with the sums of codeine concentrations in hourly patches. It was thought that the sweat patch acts as a passive reservoir for drug accumulation; however, there is evidence of loss or dynamic exchange of drugs between skin and the patch (22)(24). Our results indicated that the sum of codeine concentrations in hourly patches were generally higher than in patches worn for 1 week, indicating possible loss from patches applied for longer periods and/or dynamic exchange between the skin and the patch. Possible mechanisms include loss of codeine through the acrylate backing, and reabsorption of codeine into the stratum corneum (24). Alteration of codeine structure through metabolism or chemical degradation on the skin’s surface was not detected at the method LOQ.

Excretion of codeine in sweat occurred up to 2 weeks after the last dose. Of the weekly sweat patches worn the week after the last low and high doses, 63.6% and 70%, respectively, were positive for codeine at the method LOQ. In addition, 2 of 8 weekly sweat patches worn the second week after the last high dose contained codeine below the SAMHSA cutoff. These data provide critical information about the duration of opioid detection in sweat, an important parameter for interpreting sweat test results.

In another of our studies determining concordance between opioid excretion in urine and sweat, 28 positive weekly sweat patch results were found in the absence of a positive urine (17), 5 of which contained 6-AM above the proposed cutoff. Similarly, we examined cocaine and its metabolites in methadone maintenance patients and found discrepancies between sweat patch results and urinalyses in ~20% of cases (25).

The proposed Mandatory Guidelines for Federal Workplace Drug Testing Programs (18) indicated that sweat testing may be used for return to duty and follow-up testing because of its large window of detection and tamper-evident patch design. Sweat testing enables continuous determination of drug use outside the work environment and serves as a deterrent to future drug use. The present study comprehensively evaluated hourly and weekly sweat patches to characterize the duration, accumulation, reproducibility, time of first appearance, and dose–concentration relationship of codeine excretion in sweat, which are valuable guides for interpretation of opioid sweat results. Sweat testing is a useful alternative technique for qualitative monitoring of opioid use.


   Acknowledgments
 
This research was supported by the NIH, National Institute on Drug Abuse, Intramural Research Program. Sweat patches were donated by PharmChem, Inc. We also thank David Darwin and Deborah Price for technical assistance.


   Footnotes
 
1 Nonstandard abbreviations: 6-AM, 6-acetylmorphine; SAMHSA, Substance Abuse and Mental Health Services Administration; BSTFA +1% TMCS, N,O-bis(trimethyl)trifluoro-acetamide with 1% trimethylchlorosilane; MTBSTFA + 1% TBDMCS, N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide with 1% tert-butyldimethylchlorosilane; LOD, limit of detection; and LOQ, limit of quantification.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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A. J. Barnes, M. L. Smith, S. L. Kacinko, E. W. Schwilke, E. J. Cone, E. T. Moolchan, and M. A. Huestis
Excretion of Methamphetamine and Amphetamine in Human Sweat Following Controlled Oral Methamphetamine Administration
Clin. Chem., January 1, 2008; 54(1): 172 - 180.
[Abstract] [Full Text] [PDF]

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