Jacob Bell
New Member
Rafael de la Torre1,2,a and Simona Pichini3
1 Institut Municipal d'Investigació Mèdica (IMIM), and 2 Universitat Pompeu Fabra, Barcelona, Spain
3 Drug Research and Control Department, Istituto Superiore di Sanità , Rome, Italy
aAddress correspondence to this author at: Institut Municipal d'Investigació Mèdica (IMIM), Doctor Aiguader 80, E-08003 Barcelona, Spain. Fax 34-932213237; e-mail rtorre@imim.es.
Several reports have demonstrated that sweat is a suitable alternative biological matrix for monitoring recent drug use (1)(2). This is based on the assumption that, in the context of the absorption/distribution/metabolism/excretion (ADME) cycle of drugs, a small but sufficient fraction of a drug is excreted in sweat and can be tested. The passage of lipid-soluble compounds from blood to other fluids or matrices is regulated by the substance's pKa and by the pH of the other fluids or matices. A modified version of the Henderson—Hasselbach equation, which uses the pKa and the pH, allows theoretical calculation of the fluid-to-plasma concentration ratio (F/P ratio) (3). Drugs are generally incorporated into sweat by passive diffusion because of a concentration gradient in which only the free fraction of drug (unbound to proteins) diffuses through lipid membranes from plasma to sweat. Furthermore, because under normal conditions sweat, with a mean pH of 6.3, is more acidic than blood, basic drugs tend to accumulate in sweat.
Two approaches are currently used in testing for drugs in sweat. The first is aimed at detection of recent use of drugs (<24 h) and involves only collection of sweat at a point in time. An immunochromatographic test of the sample then provides a qualitative result (4), or drugs in sweat collected on a cotton wipe can be extracted and subjected to confirmatory analysis (5). This approach is mainly oriented to identify individuals who are under the influence of drugs. The second approach is based on patch technology and allows monitoring of illicit drug use for time windows wider than those provided by urine testing. This is because the patches can be worn for up to 1 week. Drugs accumulate in the collection device, and little or no drug degradation seems to occur during this time interval (1). Patch technology is used mainly for the follow-up of drug addicts under treatment to verify abstinence. Both approaches benefit from low invasivity and pose fewer ethical problems for sample collection than does blood or urine testing.
Until recently, the use of sweat for drug testing has been hampered by difficulties in sample recovery and by the limited sensitivities of analytical methods (6). Success in sweat testing for several drugs of abuse (4)(7)(8)(9)(10)(11)(12)(13) has been accomplished because of substantial advances in sample collection and improved accuracy of measurement methods. An important advance is the development of the sweat patch technology (14), used by Saito et al. (15) to detect {Delta}9-tetrahydrocannabinol (THC) in sweat, as reported in this issue of Clinical Chemistry. Sweat patches applied to the skin allow oxygen, carbon dioxide, and water vapor to escape, whereas the nonvolatile components, including drugs of abuse, are retained in the absorbent pad (8). Further extraction of drugs from the patch is required, but analyses are relatively easy because the chemical composition of sweat is simple compared with that of blood or urine. A variety of drugs of abuse, including opiates, cocaine, and amphetamines, have been detected in sweat by use of the patch technology (4)(8)(9)(12)(13), but little information is available concerning the presence of cannabinoids in sweat.
The detection of THC, the psychoactive component of cannabis (e.g., marijuana smoke and hashish), in sweat was first reported in 1990 (16) and subsequently found in sweat wipes from intoxicated drivers (5). In contrast to the majority of drugs of abuse, which are weak bases and tend to concentrate in biological matrices more acidic than plasma, THC is a neutral molecule and hence its diffusion is expected to be slower. Indeed, THC was found in the low ng/patch range, and 11-nor-9-carboxy-{Delta}9-tetrahydrocannabinol, the principal acidic urinary metabolite, has been never detected in sweat (17). Mandatory guidelines for federal workplace drug testing programs that were recently revised by the Substance Abuse and Mental Health Services Administration (SAMHSA) (18) address sweat testing for marijuana use. The guidelines require finding of marijuana metabolites at an initial cutoff concentration of 1.5 ng/2.5 mL of eluate (without specifying the quantity of specimen to be collected) and a confirmatory cutoff concentration of 0.5 ng/2.5 mL of eluate for THC.
In this issue of Clinical Chemistry, Saito et al. (15) describe the validation of a gas chromatographic—negative ion chemical ionization mass spectrometric method to detect THC in patches to which THC was added. The assay was initially developed based on an early confirmatory cutoff proposed by SAMHSA in December 2003 of 1 ng/patch for THC in sweat. Nonetheless, with limits of detection (LOD) and quantification (LOQ) of 0.2 ng and 0.4 ng per 2 mL of eluate, the assay has the potential of meeting the newly issued cutoff concentration. Furthermore, the authors investigated the recovery of THC from the collection pad. It appears that a substantial fraction of the drug remains bound to the pad, something expected taking into account the lipophilic nature of the drug and its avidity to glass and plastic surfaces (19).
Although the availability of analytical methods meeting administrative standards is a further step for the routine detection of THC consumption by analysis of sweat, several issues require thorough investigation as they may limit the application of THC sweat testing. Three issues must be considered: environmental skin contamination, drug absorption/loss through patch membrane, and drug reabsorption from patches.
Cannabis is the illicit drug with the highest worldwide consumption prevalence and the highest rate of positive findings in workplace drug testing. Consequently, cannabis was the first drug for which excuses were provided to explain a positive test result, an issue that was recently the subject of an Editorial in this journal (20). Sweat patches are sealed to the skin and were designed to exclude environmental contamination. In an in vitro study, Kidwell and Smith (21) showed that several drugs of abuse applied directly to the skin of drug-free individuals may persist there for several days. Neither normal hygiene nor cleaning procedures recommended before application of the sweat patch completely remove drugs deposited on skin. Thus, it might be argued that environmental contamination before patch application is a possible occurrence. Nevertheless, THC was less likely to persist on skin (22). Studies are needed of drug-free individuals exposed to environments heavily contaminated with cannabis smoke.
Some reports suggest that the patch membrane is permeable not only to gases and water vapor but, to a certain extent, to drugs (21)(23). Drugs of abuse applied on the surface of patch membrane can be absorbed, and drugs excreted in sweat may diffuse through the membrane to the outer environment. These findings suggest that membranes are more permeable than expected, although for all drugs studied, <15% of the total amount of drug present on the inner side of the membrane was able to diffuse to the outer side (21)(23). To date, the permeability of patch membranes for THC has not been studied, and investigations on this issue should be also promoted.
Finally, several studies suggest that there is a time-dependent loss of drugs during patch wearing over time. The loss of drugs of abuse from skin patches limits one of the goals of sweat patch testing: cumulative drug detection. One of the most likely mechanisms involved in drug loss is reabsorption back into the skin. This phenomenon has recently been well characterized for two basic drugs, cocaine and 3,4-methylenedioxymethamphetamine (MDMA) (4)(23). The rate of reabsorption for THC is unknown, but it could be important because the amount of drug excreted through skin is low. Whereas chronic heavy cannabis users would be easily detected, this may not be the case for recreational users, giving rise to false-negative results.
In conclusion, the report of Saito et al. (15) in this issue of Clinical Chemistry is a first relevant step for the routine detection of THC consumption through sweat testing. The stage is set for the next steps of experimental studies of environmental skin contamination and studies to characterize drug reabsorption from patches.
References
Caplan YH, Goldberger BA. Alternative specimens for workplace drug testing. J Anal Toxicol 2001;25:396-399.[Medline] [Order article via Infotrieve]
de la Torre R, Farre M, Navarro M, Pacifici R, Zuccaro P, Pichini S. Clinical pharmacokinetics of amfetamine and related substances: monitoring in conventional and non-conventional matrices. Clin Pharmacokinet 2004;43:157-185.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
Pichini S, Altieri I, Zuccaro P, Pacifici R. Drug monitoring in non-conventional biologic fluids and matrices. Clin Pharmacokinet 1996;30:211-228.[Web of Science][Medline] [Order article via Infotrieve]
Pichini S, Navarro M, Pacifici R, Zuccaro P, Ortuno J, Farre M, et al. Usefulness of sweat testing for the detection of MDMA after a single-dose administration. J Anal Toxicol 2003;27:294-303.[Medline] [Order article via Infotrieve]
Samyn N, De Boeck G, Verstraete AG. The use of oral fluid and sweat wipes for the detection of drugs of abuse in drivers. J Forensic Sci 2002;47:1380-1387.[Web of Science][Medline] [Order article via Infotrieve]
Haeckel R, Hanecke P. The application of saliva, sweat and tear fluids for diagnostic purposes. Ann Biol Clin 1993;50:903-910.
Cone EJ, Hillsgrove MJ, Jenkins AJ, Keenan RM. Sweat testing for heroin, cocaine and metabolites. J Anal Toxicol 1994;18:298-305.[Web of Science][Medline] [Order article via Infotrieve]
Burns M, Baselt RC. Monitoring drug use with a sweat patch: an experiment with cocaine. J Anal Toxicol 1995;19:41-48.[Web of Science][Medline] [Order article via Infotrieve]
Kintz P, Tracqui A, Mangin P. Sweat testing in opioid users with a sweat patch. J Anal Toxicol 1996;20:393-397.[Web of Science][Medline] [Order article via Infotrieve]
Fay J, Fogerson R, Schoendofer D, Niedbala RS, Spiehler V. Detection of methamphetamine in sweat by EIA and GC-MS. J Anal Toxicol 1996;20:398-403.[Web of Science][Medline] [Order article via Infotrieve]
Preston KL, Huestis MA, Wong CJ, Umbricht A, Goldberger BA, Cone EJ. Monitoring cocaine use in substance-abuse-treatment patients by sweat and urine testing. J Anal Toxicol 1999;23:313-322.[Web of Science][Medline] [Order article via Infotrieve]
Huestis MA, Cone EJ, Wong CJ, Umbricht A, Preston KL. Monitoring opiate use in substance abuse treatment patients with sweat and urine drug testing. J Anal Toxicol 2000;24:509-521.[Web of Science][Medline] [Order article via Infotrieve]
Moody DE, Spanbauer AC, Taccogno JL, Smith EK. Comparative analysis of sweat patches for cocaine (and metabolites) by radioimmunoassay and gas chromatography-positive ion chemical ionization-mass spectrometry. J Anal Toxicol 2004;28:86-93.[Medline] [Order article via Infotrieve]
Fogerson R, Schoendorfer D, Fay J, Spiehler V. Qualitative detection of opiates in sweat by EIA and CG-MS. J Anal Toxicol 1997;21:451-457.[Web of Science][Medline] [Order article via Infotrieve]
Saito T, Wtsadik A, Scheidweiler KB, Fortner N, Takeichi S, Huestis MA. Validated gas chromatographic—negative ion chemical ionization mass spectrometric method for {Delta}9-tetrahydrocannabinol in sweat patches. Clin Chem 2004;50:2083-2090.[Abstract/Free Full Text]
Balabanova S, Schneider E. Detection of drugs in sweat. Beitr Gerichtl Med 1990;48:45-49.[Medline] [Order article via Infotrieve]
Staub C. Chromatographic procedures for determination of cannabinoids in biological samples, with special attention to blood and alternative matrices like hair, saliva, sweat and meconium. J Chromatogr B Biomed Sci Appl 1999;733:119-126.[Medline] [Order article via Infotrieve]
Department of Health and Human Services. Substance Abuse and Mental Health Administration. Mandatory guidelines for federal workplace drug testing. The Substance Abuse and Mental Health Services Administration - Homepage (accessed August 2004)..
Christophersen AS. Tetrahydrocannabinol stability in whole blood: plastic versus glass containers. J Anal Toxicol 1986;10:129-131.[Web of Science][Medline] [Order article via Infotrieve]
ElSohly MA. Practical challenge to positive drug tests for marijuana [Editorial]. Clin Chem 2003;49:1037-1038.[Free Full Text]
Kidwell DA, Smith FP. Susceptibility of PharmChek drugs of abuse patch to environmental contamination. Forensic Sci Int 2001;116:89-106.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
Kidwell DA, Holland JC, Athanaselis S. Testing for drugs of abuse in saliva and sweat. J Chromatogr B Biomed Sci Appl 1998;713:111-135.[CrossRef][Medline] [Order article via Infotrieve]
Uemura N, Nath RP, Harkey MR, Henderson GL, Mendelson J, Jones RT. Cocaine levels in sweat collection patches vary by location of patch placement and decline over time. J Anal Toxicol 2004;28:253-259.[Web of Science][Medline] [Order article via Infotrieve]
Source: Usefulness of Sweat Testing for the Detection of Cannabis Smoke
1 Institut Municipal d'Investigació Mèdica (IMIM), and 2 Universitat Pompeu Fabra, Barcelona, Spain
3 Drug Research and Control Department, Istituto Superiore di Sanità , Rome, Italy
aAddress correspondence to this author at: Institut Municipal d'Investigació Mèdica (IMIM), Doctor Aiguader 80, E-08003 Barcelona, Spain. Fax 34-932213237; e-mail rtorre@imim.es.
Several reports have demonstrated that sweat is a suitable alternative biological matrix for monitoring recent drug use (1)(2). This is based on the assumption that, in the context of the absorption/distribution/metabolism/excretion (ADME) cycle of drugs, a small but sufficient fraction of a drug is excreted in sweat and can be tested. The passage of lipid-soluble compounds from blood to other fluids or matrices is regulated by the substance's pKa and by the pH of the other fluids or matices. A modified version of the Henderson—Hasselbach equation, which uses the pKa and the pH, allows theoretical calculation of the fluid-to-plasma concentration ratio (F/P ratio) (3). Drugs are generally incorporated into sweat by passive diffusion because of a concentration gradient in which only the free fraction of drug (unbound to proteins) diffuses through lipid membranes from plasma to sweat. Furthermore, because under normal conditions sweat, with a mean pH of 6.3, is more acidic than blood, basic drugs tend to accumulate in sweat.
Two approaches are currently used in testing for drugs in sweat. The first is aimed at detection of recent use of drugs (<24 h) and involves only collection of sweat at a point in time. An immunochromatographic test of the sample then provides a qualitative result (4), or drugs in sweat collected on a cotton wipe can be extracted and subjected to confirmatory analysis (5). This approach is mainly oriented to identify individuals who are under the influence of drugs. The second approach is based on patch technology and allows monitoring of illicit drug use for time windows wider than those provided by urine testing. This is because the patches can be worn for up to 1 week. Drugs accumulate in the collection device, and little or no drug degradation seems to occur during this time interval (1). Patch technology is used mainly for the follow-up of drug addicts under treatment to verify abstinence. Both approaches benefit from low invasivity and pose fewer ethical problems for sample collection than does blood or urine testing.
Until recently, the use of sweat for drug testing has been hampered by difficulties in sample recovery and by the limited sensitivities of analytical methods (6). Success in sweat testing for several drugs of abuse (4)(7)(8)(9)(10)(11)(12)(13) has been accomplished because of substantial advances in sample collection and improved accuracy of measurement methods. An important advance is the development of the sweat patch technology (14), used by Saito et al. (15) to detect {Delta}9-tetrahydrocannabinol (THC) in sweat, as reported in this issue of Clinical Chemistry. Sweat patches applied to the skin allow oxygen, carbon dioxide, and water vapor to escape, whereas the nonvolatile components, including drugs of abuse, are retained in the absorbent pad (8). Further extraction of drugs from the patch is required, but analyses are relatively easy because the chemical composition of sweat is simple compared with that of blood or urine. A variety of drugs of abuse, including opiates, cocaine, and amphetamines, have been detected in sweat by use of the patch technology (4)(8)(9)(12)(13), but little information is available concerning the presence of cannabinoids in sweat.
The detection of THC, the psychoactive component of cannabis (e.g., marijuana smoke and hashish), in sweat was first reported in 1990 (16) and subsequently found in sweat wipes from intoxicated drivers (5). In contrast to the majority of drugs of abuse, which are weak bases and tend to concentrate in biological matrices more acidic than plasma, THC is a neutral molecule and hence its diffusion is expected to be slower. Indeed, THC was found in the low ng/patch range, and 11-nor-9-carboxy-{Delta}9-tetrahydrocannabinol, the principal acidic urinary metabolite, has been never detected in sweat (17). Mandatory guidelines for federal workplace drug testing programs that were recently revised by the Substance Abuse and Mental Health Services Administration (SAMHSA) (18) address sweat testing for marijuana use. The guidelines require finding of marijuana metabolites at an initial cutoff concentration of 1.5 ng/2.5 mL of eluate (without specifying the quantity of specimen to be collected) and a confirmatory cutoff concentration of 0.5 ng/2.5 mL of eluate for THC.
In this issue of Clinical Chemistry, Saito et al. (15) describe the validation of a gas chromatographic—negative ion chemical ionization mass spectrometric method to detect THC in patches to which THC was added. The assay was initially developed based on an early confirmatory cutoff proposed by SAMHSA in December 2003 of 1 ng/patch for THC in sweat. Nonetheless, with limits of detection (LOD) and quantification (LOQ) of 0.2 ng and 0.4 ng per 2 mL of eluate, the assay has the potential of meeting the newly issued cutoff concentration. Furthermore, the authors investigated the recovery of THC from the collection pad. It appears that a substantial fraction of the drug remains bound to the pad, something expected taking into account the lipophilic nature of the drug and its avidity to glass and plastic surfaces (19).
Although the availability of analytical methods meeting administrative standards is a further step for the routine detection of THC consumption by analysis of sweat, several issues require thorough investigation as they may limit the application of THC sweat testing. Three issues must be considered: environmental skin contamination, drug absorption/loss through patch membrane, and drug reabsorption from patches.
Cannabis is the illicit drug with the highest worldwide consumption prevalence and the highest rate of positive findings in workplace drug testing. Consequently, cannabis was the first drug for which excuses were provided to explain a positive test result, an issue that was recently the subject of an Editorial in this journal (20). Sweat patches are sealed to the skin and were designed to exclude environmental contamination. In an in vitro study, Kidwell and Smith (21) showed that several drugs of abuse applied directly to the skin of drug-free individuals may persist there for several days. Neither normal hygiene nor cleaning procedures recommended before application of the sweat patch completely remove drugs deposited on skin. Thus, it might be argued that environmental contamination before patch application is a possible occurrence. Nevertheless, THC was less likely to persist on skin (22). Studies are needed of drug-free individuals exposed to environments heavily contaminated with cannabis smoke.
Some reports suggest that the patch membrane is permeable not only to gases and water vapor but, to a certain extent, to drugs (21)(23). Drugs of abuse applied on the surface of patch membrane can be absorbed, and drugs excreted in sweat may diffuse through the membrane to the outer environment. These findings suggest that membranes are more permeable than expected, although for all drugs studied, <15% of the total amount of drug present on the inner side of the membrane was able to diffuse to the outer side (21)(23). To date, the permeability of patch membranes for THC has not been studied, and investigations on this issue should be also promoted.
Finally, several studies suggest that there is a time-dependent loss of drugs during patch wearing over time. The loss of drugs of abuse from skin patches limits one of the goals of sweat patch testing: cumulative drug detection. One of the most likely mechanisms involved in drug loss is reabsorption back into the skin. This phenomenon has recently been well characterized for two basic drugs, cocaine and 3,4-methylenedioxymethamphetamine (MDMA) (4)(23). The rate of reabsorption for THC is unknown, but it could be important because the amount of drug excreted through skin is low. Whereas chronic heavy cannabis users would be easily detected, this may not be the case for recreational users, giving rise to false-negative results.
In conclusion, the report of Saito et al. (15) in this issue of Clinical Chemistry is a first relevant step for the routine detection of THC consumption through sweat testing. The stage is set for the next steps of experimental studies of environmental skin contamination and studies to characterize drug reabsorption from patches.
References
Caplan YH, Goldberger BA. Alternative specimens for workplace drug testing. J Anal Toxicol 2001;25:396-399.[Medline] [Order article via Infotrieve]
de la Torre R, Farre M, Navarro M, Pacifici R, Zuccaro P, Pichini S. Clinical pharmacokinetics of amfetamine and related substances: monitoring in conventional and non-conventional matrices. Clin Pharmacokinet 2004;43:157-185.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
Pichini S, Altieri I, Zuccaro P, Pacifici R. Drug monitoring in non-conventional biologic fluids and matrices. Clin Pharmacokinet 1996;30:211-228.[Web of Science][Medline] [Order article via Infotrieve]
Pichini S, Navarro M, Pacifici R, Zuccaro P, Ortuno J, Farre M, et al. Usefulness of sweat testing for the detection of MDMA after a single-dose administration. J Anal Toxicol 2003;27:294-303.[Medline] [Order article via Infotrieve]
Samyn N, De Boeck G, Verstraete AG. The use of oral fluid and sweat wipes for the detection of drugs of abuse in drivers. J Forensic Sci 2002;47:1380-1387.[Web of Science][Medline] [Order article via Infotrieve]
Haeckel R, Hanecke P. The application of saliva, sweat and tear fluids for diagnostic purposes. Ann Biol Clin 1993;50:903-910.
Cone EJ, Hillsgrove MJ, Jenkins AJ, Keenan RM. Sweat testing for heroin, cocaine and metabolites. J Anal Toxicol 1994;18:298-305.[Web of Science][Medline] [Order article via Infotrieve]
Burns M, Baselt RC. Monitoring drug use with a sweat patch: an experiment with cocaine. J Anal Toxicol 1995;19:41-48.[Web of Science][Medline] [Order article via Infotrieve]
Kintz P, Tracqui A, Mangin P. Sweat testing in opioid users with a sweat patch. J Anal Toxicol 1996;20:393-397.[Web of Science][Medline] [Order article via Infotrieve]
Fay J, Fogerson R, Schoendofer D, Niedbala RS, Spiehler V. Detection of methamphetamine in sweat by EIA and GC-MS. J Anal Toxicol 1996;20:398-403.[Web of Science][Medline] [Order article via Infotrieve]
Preston KL, Huestis MA, Wong CJ, Umbricht A, Goldberger BA, Cone EJ. Monitoring cocaine use in substance-abuse-treatment patients by sweat and urine testing. J Anal Toxicol 1999;23:313-322.[Web of Science][Medline] [Order article via Infotrieve]
Huestis MA, Cone EJ, Wong CJ, Umbricht A, Preston KL. Monitoring opiate use in substance abuse treatment patients with sweat and urine drug testing. J Anal Toxicol 2000;24:509-521.[Web of Science][Medline] [Order article via Infotrieve]
Moody DE, Spanbauer AC, Taccogno JL, Smith EK. Comparative analysis of sweat patches for cocaine (and metabolites) by radioimmunoassay and gas chromatography-positive ion chemical ionization-mass spectrometry. J Anal Toxicol 2004;28:86-93.[Medline] [Order article via Infotrieve]
Fogerson R, Schoendorfer D, Fay J, Spiehler V. Qualitative detection of opiates in sweat by EIA and CG-MS. J Anal Toxicol 1997;21:451-457.[Web of Science][Medline] [Order article via Infotrieve]
Saito T, Wtsadik A, Scheidweiler KB, Fortner N, Takeichi S, Huestis MA. Validated gas chromatographic—negative ion chemical ionization mass spectrometric method for {Delta}9-tetrahydrocannabinol in sweat patches. Clin Chem 2004;50:2083-2090.[Abstract/Free Full Text]
Balabanova S, Schneider E. Detection of drugs in sweat. Beitr Gerichtl Med 1990;48:45-49.[Medline] [Order article via Infotrieve]
Staub C. Chromatographic procedures for determination of cannabinoids in biological samples, with special attention to blood and alternative matrices like hair, saliva, sweat and meconium. J Chromatogr B Biomed Sci Appl 1999;733:119-126.[Medline] [Order article via Infotrieve]
Department of Health and Human Services. Substance Abuse and Mental Health Administration. Mandatory guidelines for federal workplace drug testing. The Substance Abuse and Mental Health Services Administration - Homepage (accessed August 2004)..
Christophersen AS. Tetrahydrocannabinol stability in whole blood: plastic versus glass containers. J Anal Toxicol 1986;10:129-131.[Web of Science][Medline] [Order article via Infotrieve]
ElSohly MA. Practical challenge to positive drug tests for marijuana [Editorial]. Clin Chem 2003;49:1037-1038.[Free Full Text]
Kidwell DA, Smith FP. Susceptibility of PharmChek drugs of abuse patch to environmental contamination. Forensic Sci Int 2001;116:89-106.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
Kidwell DA, Holland JC, Athanaselis S. Testing for drugs of abuse in saliva and sweat. J Chromatogr B Biomed Sci Appl 1998;713:111-135.[CrossRef][Medline] [Order article via Infotrieve]
Uemura N, Nath RP, Harkey MR, Henderson GL, Mendelson J, Jones RT. Cocaine levels in sweat collection patches vary by location of patch placement and decline over time. J Anal Toxicol 2004;28:253-259.[Web of Science][Medline] [Order article via Infotrieve]
Source: Usefulness of Sweat Testing for the Detection of Cannabis Smoke
