Sweat Patch Research Articles

Delayed disposition of cocaine in sweat patches and in skin blister: cocaine may migrate from plasma to sweat patches via interstitial fluid

Sweat patch analysis is extensively used for drug abuse monitoring. The present study investigates how cocaine migrates to sweat patches. In the cumulative collection model, the drug absorption rate in patches should be proportional to the drug concentration in the preceding disposition compartment if drug back-transfer is negligible. Therefore, we measured the slopes of cocaine concentration curves in patches as a marker for absorption rate (into patches) after a single dose of cocaine-d5 (1mg/kg over 60 min) in healthy cocaine users (n=5). Patches were placed on the back of subjects prior to drug administration and removed at 0–72 hr postdose. Blood and interstitial fluid (skin blister fluid) were collected up to 72 hr. Patch cocaine levels showed semi-cumulative collection with peaks between 8 and 48 hr. Cocaine levels in plasma and interstitial fluid peaked at 1.0±0 and 5.3±0.6 hours postdose, respectively, suggesting a delayed cocaine disposition in the interstitial fluid. Similarly, patch cocaine absorption was delayed with rate peaks at 4.3±2.9 hr postdose. Tmax for plasma benzoylecgonine (BE) was 5.0±2.4 hr. BE also showed a delayed peak in the interstitial fluid at 11.3±11.0 hr post, and the highest BE absorption in patches was observed in a similar time range of 12.4±4.9 hr. Cocaine and its metabolite migrate into patches in a time period that coincides with Tmax in interstitial fluid. Cocaine seems to travel from plasma to sweat patches via interstitial fluid. Clinical Pharmacology & Therapeutics (2004) 75, P44–P44; doi: 10.1016/j.clpt.2003.11.163

Detecting crack and other cocaine use with fastpatches.

A continuing social problem is presented by the large number of individuals who use crack cocaine. Recent research has identified unique pyrolysis products of crack or burned cocaine as anhydroecgonine methylester (AEME) and ecgonidine (ECD) through gas chromatography/mass spectrometry (GC/MS) that allow for the detection of crack use distinct from other cocaine use. However, there have been no large-scale studies to document the presence and prevalence of these substances in sweat. A new sweat-testing appliance called a fastpatch was developed for this study. Through mild heating and a slightly larger collection pad than a standard Pharmchek( trade mark ) sweat patch, this product shows the promise of shorter required wear periods than standard sweat patches, and possibly longer time-periods of detected use. One hundred and eighty subjects wore 360 fastpatch prototypes (one per hand). However, subsequent analysis determined that only one patch per subject was needed to obtain sufficient sweat eluate for GC/MS. Cocaine use was detected in sweat of 92% of subjects through GC/MS, comparing favorably with 91% with EMIT urinalysis. Crack metabolites were detected in 54% of subjects. The predominant analyte detected was AEME. There were no significant differences in detection rates between 15-, 20- and 30-minute wear periods. All wear periods detected both cocaine use in general and crack use successfully. These results suggest that crack use as distinct from other cocaine use can be detected in sweat and that fastpatches are a promising new way to detect drugs of abuse.

Comparison of daily urine, sweat, and skin swabs among cocaine users

This study (1) compares urine, skin swabs, and PharmChek™ sweat patches for monitoring drug use; (2) measures possible environmental contamination in recent cocaine (COC) users; and (3) evaluates various immunoassays (IA) for screening COC in diverse matrices. Unique aspects include daily urine monitoring of 10 participants for 4 weeks, multiple monitoring methods, analysis for all specimens by IA and gas chromatography (GC)/mass spectrometry (MS), and the potential for continued illicit drug use by participants. Urine served as the “gold standard” specimen for determining drug use. Only cocaine and related substances were detected. Trace amounts of drugs were found on the skin (<50 ng per swab) of urine-negative participants’ hands or forehead. In contrast, larger quantities of COC were found on the skin of individuals with BE-positive urines or individuals living with drug users (up to 20 μg per swab). Patch COC amounts among the three regular users (250–9000, 0–240, 160–22,000 ng per patch) exceeded BE (50–950, none, 30–2200 ng per patch). Pre-swabs, valuable for interpreting the source or time frame of positive patch results, contained substantial COC (38–1160, 0–152, 34–762 ng per swab) prior to patch application; therefore, patch results may represent current use, prior use, contamination, or a combination. In three individuals with no indication of cocaine use, false positives (defined as sweat patch positive when urine specimens were <300 ng BE/ml) occurred at a 7% rate. Proposed cut-off concentrations of 75 ng cocaine per patch and 300 ng BE/ml urine curtail the incidence of false positives in this limited population. Three immunoassays were compared to screen specimens for cocaine: a modified, manual Microgenics CEDIA; a Cozart ELISA; and an OraSure ELISA. CEDIA’s limit of detection (LOD) was 81 ng/ml, compared with LODs of 4 ng/ml for the Cozart ELISA and 1.5 ng/ml for the OraSure ELISA. Cozart correlated with OraSure results for COC concentrations <2000 ng per swab ( n=117), r 2=0.79.

Tests for Drugs of Abuse

Tests for Drugs of Abuse

Comparison of urine to sweat patch test results in court ordered testing

A former cocaine and methamphetamine abuser was continuously monitored with both sweat patch and urine testing for approximately 6 months. Thirteen sweat patches were applied and collected, five were positive for cocaine and/or methamphetamine, but all the urine specimens collected were negative at the analytical cut-off levels. The high incidence of false positive sweat patch tests in relation to the sensitivity, specificity, and efficiency of the sweat patch assay is discussed. Possible mechanisms, which can lead to false positive results, are presented. The results of our study raise further questions about the preferential use of the sweat patch in detecting new episodes of drug use in formerly chronic drug users.

SWEAT AND SODIUM LOSSES IN CRAMP-PRONE PROFESSIONAL FOOTBALL PLAYERS

Severe, debilitating muscle cramping is often associated with large fluid and sweat sodium losses. Our purpose was to determine whether or not sweat [Na+] and large fluid losses were associated in cramp-prone professional football players (N = 3). Players were referred for testing due to frequent cramping problems and were interviewed for history of severe muscle cramps in the lower extremities or whole body during pre-season preparation. Since pre-collegiate play, all players had experienced frequent, intense muscle cramps during explosive movements. Change in bodyweight and site-specific sweat patches were used to measure gross sweat loss and estimate mean whole-body sweat rate and sweat electrolyte values during one hour of cycle exercise (workload ≈ 150 W) in a warm environment (80°F, 50% RH) while wearing shorts.TableThese players showed large inter-individual variability in sweat rates and sweat [Na+]. Longer practices in full uniform and in hotter, more humid conditions than those of our one-hour study are likely to increase the risk for larger sweat and sodium losses and the potential for heat-related illness and cramping. While the association between muscle cramps and fluid/sodium losses has yet to be fully elucidated, these data do support that large fluid and sodium losses may be evidenced in players with a history of muscle cramps.

Susceptibility of PharmChek™ drugs of abuse patch to environmental contamination

The key component of the PharmChek™ sweat patch, the membrane, has been tested for the passage of externally applied materials. Drugs in the uncharged state rapidly penetrated the membrane but charged species were greatly slowed. In basic media, detectable concentrations of cocaine, methamphetamine, and heroin were observed at the earliest collection time (ca. 30 s), after drugs were placed on the outside of the membrane. Drug concentrations increased over the 2 h time course, when amounts detected (1710 ng cocaine, 1060 ng methamphetamine, 550 ng heroin per pad at 2 h) represented 5–17% of the drug deposited on the surface of the sweat patch. Drugs externally applied to human skin were shown to bind readily. Drugs deposited on the skin of drug-free volunteers several days prior to application of the sweat patch were not completely removed by normal hygiene or the cleaning procedures recommended before application of the sweat patch. Even 6 days of normal hygiene did not remove all drugs from externally contaminated skin and positive sweat patches resulted. A mechanism for passage of drugs through the sweat patch membrane, a mechanism for retention of drugs on skin, and a redesign of the sweat patch and modification of its use to reduce external contamination are proposed. Appropriate care should be taken in the interpretation of positive results from a sweat patch test until more research is conducted.

Drug deposition in adipose tissue and skin: evidence for an alternative source of positive sweat patch tests

In a series of licit and illicit drug-related deaths, qualitative and quantitative analyses on extracts of adipose tissue and skin were performed by GC/MS. In all cases, the adipose tissue was found to contain drugs at concentrations lower than, approximately equal to, or even greater than the concentrations of the same analytes found in the blood, which may reflect a consequence of long-term chronic exposure, or acute intoxication, or some combination of both. Approximately one cubic inch of skin with adipose tissue was removed from the mid to lower abdominal region adjacent to the midline incision during autopsy. The drugs were recovered from the specimens following incubation and alkaline, acidic, and alkaline chloroform back extraction of one to three grams of tissue. Deuterated analogs of the analytes were added to the matrix at the beginning of the incubation period. Cocaine and free morphine (from heroin) were readily identified in several cases. The presence of these illicit drugs in adipose tissue raises significant forensic questions, especially the use of ‘sweat patches’ to monitor recent cocaine or heroin use in chronic drug users.

Clozapine dose–concentration relationships in plasma, hair and sweat specimens of schizophrenic patients

The aim of the present study was to establish an analytical method for the determination of clozapine in sweat and to determine whether the clozapine level in hair and sweat were correlated to the daily dose of clozapine delivered to patients. Twenty-six subjects treated with clozapine at 200–700 mg/day for refractory psychosis were included in the study. Clozapine was determined in plasma by liquid chromatography coupled to a diode array detection system, after extraction with an organic solvent at pH 9.5. Clozapine was extracted from hair and sweat patches specimens by incubation in methanol overnight at 40°C. The residues were analyzed by gas chromatography coupled to mass spectrometry in the electronic impact mode of detection. It was possible to determine clozapine in concentrations ranging from 30 to 1016 ng/ml in plasma (n=22), from 0.17 to 34.24 ng/mg in hair (n=23) and from 49 to 5609 ng/patch in sweat (n=20). Preliminary results suggest a lack of correlation between daily regimen of clozapine and plasma levels of the drug. Therefore, a better dose–concentration relationship was observed in our study between daily dose and hair concentration (r=0.542, P<7%) or between daily dose and sweat concentration (r=0.589, P<6%), but with wide variations for patients at the same posology. However, the idea of using quantitative drug measurements in hair or sweat to ascertain whether a patient has taken his treatment exactly as prescribed will remain inapplicable.

Drug Testing with Alternative Matrices II. Mechanisms of Cocaine and Codeine Deposition in Hair

A 10-week inpatient study was performed to evaluate cocaine, codeine, and metabolite disposition in biological matrices collected from volunteers. An initial report described drug disposition in plasma, sebum, and stratum corneum collected from five African-American males. This report focuses on drug disposition in hair and sweat collected from the same five subjects. Following a three-week washout period, three doses of cocaine HCl (75 mg/70 kg, subcutaneous) and three doses of codeine SO4 (60 mg/70 kg, oral) were administered on alternating days in week 4 (low-dose week). The same dosing sequence was repeated in week 8 with doubled doses (high-dose week). Hair was collected by shaving the entire scalp once each week. Hair from the anterior vertex was divided into two portions. One portion was washed with isopropanol and phosphate buffer; the other portion was not washed. Hair was enzymatically digested, samples were centrifuged, and the supernatant was collected. Sweat was collected periodically by placing PharmChek sweat patches on the torso. Drugs were extracted from sweat patches with methanol/0.2 M sodium acetate buffer (75:25, v/v). Supernatants from hair digests, hair washes, and sweat patch extracts were processed by solid-phase extraction followed by gas chromatography-mass spectrometry analysis for cocaine, codeine, 6-acetylmorphine, and metabolites. Cocaine and codeine were the primary analytes identified in sweat patches and hair. Drugs were detected in sweat within 8 h after dosing, and drug secretion primarily occurred within 24 h after dosing. No clear relationship was observed between dose and drug concentrations in sweat. Drug incorporation into hair appeared to be dose-dependent. Drugs were detected in hair within 1-3 days after the last drug administration; peak drug concentrations generally occurred in the following 1-2 weeks; thereafter, drug concentrations decreased. Solvent washes removed 50-55% of cocaine and codeine from hair collected 1-3 days after the last drug dose. These data may reflect removal of drug that was deposited by sweat shortly after dosing. Drug removed by washing hair collected 1-3 weeks after the last dose was minimal for cocaine but variable for codeine. Drug in these specimens was likely transferred from blood to germinative hair cells followed by emergence of drug in growing hair. These findings suggest that drug deposition in hair occurs by multiple mechanisms.

Monitoring Cocaine Use in Substance-Abuse-Treatment Patients by Sweat and Urine Testing

Sweat and urine specimens were collected from 44 methadone-maintenance patients to evaluate the use of sweat testing to monitor cocaine use. Paired sweat patches that were applied and removed weekly (on Tuesdays) were compared with 3-5 consecutive urine specimens collected Mondays, Wednesdays, and Fridays. All patches (N = 930) were extracted in 2.5 mL of solvent and analyzed by ELISA immunoassay (cutoff concentration 10 ng/mL); a subset of patches (N = 591) was also analyzed by gas chromatography-mass spectrometry (GC-MS) for cocaine, benzoylecgonine (BZE), and ecgonine methyl ester (EME) (cutoff concentration 5 ng/mL). Urine specimens were subjected to qualitative analysis by EMIT (cutoff 300 ng/mL) and subsets were analyzed by TDx (semiquantitative, LOD 30 ng/mL) and by GC-MS for cocaine (LOD 5 ng/mL). Results were evaluated to (1) determine the relative amounts of cocaine and its metabolites in sweat; (2) assess replicability in duplicate patches; (3) compare ELISA and GC-MS results for cocaine in sweat; and (4) compare the detection of cocaine use by sweat and urine testing. Cocaine was detected by GC-MS in 99% of ELISA-positive sweat patches; median concentrations of cocaine, BZE, and EME were 378, 78.7, and 74 ng/mL, respectively. Agreement in duplicate patches was approximately 90% by ELISA analysis. The sensitivity, specificity, and efficiency of sweat ELISA cocaine results as compared with sweat GC-MS results were 93.6%, 91.3%, and 93.2%, respectively. The sensitivity, specificity, and efficiency between ELISA sweat patch and EMIT urine results were 97.6%, 60.5%, and 77.7%, respectively. These results support the use of sweat patches for monitoring cocaine use, though further evaluation is needed.

Caffeine demethylation monitoring using a transdermal sweat patch.

Caffeine and two metabolites (paraxanthine and theobromine) were quantitated by high-performance liquid chromatography (HPLC) using extracts from transdermal sweat patches that continuously collected and stored analytes lost through the skin. Following caffeine consumption, remarkably clean chromatograms were obtained with minimal sample preparation. Caffeine and paraxanthine accumulated in the patch at comparable rates, and theobromine accumulated more slowly. A major urinary metabolite, 1-methylxanthine, was notably absent in sweat-patch and plasma extracts, a finding which favors a renal source for this metabolite. A simple, noninvasive approximation of N-demethylation can be made by calculating the paraxanthine/ caffeine and theobromine/caffeine ratios in the patch extract. These ratios were significantly reduced in high-dose (600 mg) versus low-dose (200 mg) subjects, possibly reflecting a decreased clearance of caffeine. Because the sweat patches can be worn for several days, the technique gives a multiday historical record which reflects the fluctuating systemic concentration of caffeine and its hepatic metabolites and thus might be useful to noninvasively monitor compliance by caffeine-restricted patients or to assess drug-metabolizing status.

Codeine testing in sweat and saliva with the Drugwipe.

With the growing interest in drug testing within different sectors of society, there has become a need for drug assays that can be performed immediately at the site of specimen collection. Recently, Securetec (Ottobrunn, Germany) has introduced the Drugwipe, a non instrument-based, on-site immunodiagnostic assay for the detection of drugs on surfaces. Different tests are available for opiates, cocaine and cannabis. To document the applications of the Drugwipe "opiate" on human biological fluids, 60 mg codeine phosphate were orally administered to 6 subjects. First, sweat testing with the Drugwipe was studied. The wiping section of the kit was used to swab the forehead of the subjects for 10 s, at 1, 4, 9 and 24 h after codeine administration. At the same time, for each period, a sweat patch (Pharmchek, USA) was applied to the outer portion of the upper arm. Codeine was then quantified in the patch by GC/MS and the measured concentrations used as reference. In all subjects except one the Drugwipe tested positive for opiates, however with few false negative results. In the second part of the study, results of the Drugwipe were compared with those obtained by GC/MS for saliva. The tongue of the subjects was carefully wiped over a period 24 h, and at the same time a specimen of saliva collected. Although codeine could be detected using the Drugwipe, numerous false negative results were observed. Codeine tested positive by GC/MS but remained negative using the Drugwipe in several cases. This can be explained by a codeine concentration which was too low to show positive with the Drugwipe, interfering substances may be present in saliva or the sampling procedure is inadequate.

Nicotine monitoring in sweat with a sweat patch

In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional samples, such as sweat. In a study conducted with cigarettes smokers and nonsmokers, PharmChek sweat patches were applied to 29 subjects for 72 h. Nicotine was extracted in 5 ml methanol in the presence of 200 ng nicotine-d 4, used as internal standard. After 20 min agitation, the methanolic solution was evaporated to dryness in the presence of 10 μl octanol to ensure nonvolatility of nicotine. Nicotine was determined using gas chromatography coupled to mass spectrometry after separation on a 30-m capillary HP5 MS column. The assay was linear in the range 50–2500 ng/patch, with an extraction recovery of 76±5%. Limit of detection was 10 ng/patch. Nicotine concentrations in sweat were not detected for the nonexposed nonsmokers ( n=8), 87 to 266 ng/patch for the passive smokers ( n=6) and 150 to 2498 ng/patch for the smokers ( n=15). This study demonstrated a useful application of the sweat patch for monitoring tobacco exposure.

Enantioselective analysis of methadone in sweat as monitored by liquid chromatography/ion spray-mass spectrometry.

In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional samples, such as sweat. In a study conducted during a methadone maintenance program, PharmChek sweat patches were applied to 20 subjects. The subjects were orally administered methadone in 1 dosage/day, and doses ranged from 80 to 100 mg. The sweat patch was applied 10 minutes before administration and removed 72 hours later just before a new administration of methadone. The absorbent pad was stored at -20 degrees C until analysis in plastic tubes. Methadone was extracted in 5 ml methanol in presence of 200 ng of racemic methadone-d3, used as internal standard. After a 30-minute agitation, the methanol solution was evaporated to dryness. Enantioselective separation of methadone was obtained using an alpha-1-acid glycoprotein column (100 x 4 mm ID) and liquid chromatography/ion spray-mass spectrometry. In all 20 specimens obtained from subjects under racemic methadone treatment, R- (the active form) and S-enantiomers of methadone were identified with the following concentrations: 26 to 1118 ng/patch for R-methadone and 28 to 1114 ng/patch for S-methadone. The ratio between R- and S-methadone was in the range of 0.72 to 2.66 and was higher than 1.00 in 15 samples. No correlation between the doses of methadone administered and the concentrations of methadone in sweat was observed.

Qualitative detection of opiates in sweat by EIA and GC-MS.

Sweat was collected with the PharmChek sweat patch, and drugs were eluted from the collection pad of the patch. A solid-phase enzyme immunoassay (EIA) using microtiter plates was modified for the analysis of opiates in sweat. After opiate administration, sweat contains primarily parent opiate (heroin, codeine) and lipophilic metabolites (6-monoacetylmorphine [6-MAM]). The immunoassay was determined to have a cross-reactivity with codeine of 588%, with hydrocodone of 143%, with diacetylmorphine of 28%, and with 6-MAM of 30% relative to 100% for the morphine calibrators. The optimum cutoff concentration for this modified assay was determined by receiver operator characteristic analysis using 215 patches from 95 subjects to be 10 ng/mL morphine equivalents. At this cutoff concentration the assay had a diagnostic sensitivity of 86.9% and a diagnostic specificity of 92.8% versus gas chromatography-mass spectrometry (GC-MS), which was the reference method. The positive predictive value at a prevalence of 50% was 86%. The intra-assay precision at 10 ng/mL was 7.8%, and the interassay coefficient of variation (CV) was 39%. Analysis of spiked patches around the cutoff gave a percent positive threshold of approximately 50% between 10 and 15 ng/mL and a 95% confidence level for a positive result by the EIA between 20 and 25 ng/mL. Eighteen possible adulterants that could be injected into or under the patch were studied. Two (tile cleaner and detergent) can cause false-positive responses in the immunoassay. Two adulterants reduced response to spiked drug (Visine eye drops and Ben Gay ointment), which could cause a false-negative response. All results were confirmed by GC-MS. The clinical sensitivity and specificity for detecting drug use by analyzing sweat collected from human subjects following known doses of codeine (0, 30, and 60 mg orally) or heroin (20 mg intravenously) were 76 and 100%, respectively.

Sweat testing for heroin and metabolites in a heroin maintenance program

Recent advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional biological materials such as sweat. In a study conducted during a heroin maintenance program, 14 subjects had sweat patches applied, then received intravenously two or three doses of heroin hydrochloride ranging from 80 to 1000 mg/day. The sweat patch was applied 10 min before the first dosage and removed approximately 24 h later, minutes before the next dosage. Absorbent pads were stored at -20 degrees C in plastic tubes until analysis. The target drugs were extracted in 5 mL of acetonitrile in the presence of 100 ng each of heroin-d9, 6-acetylmorphine-d3, and morphine-d3. After agitation for 30 min, the acetonitrile solution was divided into two portions: 2 mL for heroin testing and the remainder for testing for the other compounds. After evaporation, the residue of the first portion was reconstituted in 35 microL of acetonitrile; the second was derivatized by silylation with 40 microL of N,O-bis(trimethylsilyl)trifluoroacetamide containing 10 mL/L trimethylchlorosilane. Drugs were analyzed by GC-MS in electron impact mode. Concentrations (nanograms per patch) ranged from 2.1 to 96.3 for heroin, 0 to 24.6 for 6-acetylmorphine, and 0 to 11.2 morphine. Except in one case, heroin was the major drug present in sweat, followed by 6-acetylmorphine and morphine. We observed no correlation between the doses of heroin administered and the concentrations of heroin measured in sweat.

Preliminary Practical Findings on Drug Monitoring by a Transcutaneous Collection Device

A noninvasive and nonocclusive skin patch (Sudormed) was investigated for the systematic collection of drugs of abuse over a period of several days. First, the applicability and user friendliness were tested by volunteers. The permeability of the polyurethane dressing from the outside to the inside for an aqueous solution was shown by incubating the outside layer with Rhodamine B. No fluorescence could be detected in the cotton pad beneath. A single dose experiment using theophylline as a model compound showed that there was a delay in time before the substance could be determined in the pad. The drug content decreased with increasing time of patch application. When eight volunteers participating in a methadone treatment were monitored, the substitute drug could always be detected in the patch associated with a minor concentration of EDDP. Besides, in some of the patches investigated, indications for an abuse of cocaine and heroin were found. The so-called sweat patch appears to be a valuable tool in clinical and forensic toxicology, as it offers a longer and prospective surveillance period compared with blood and urine testing.

Detection of methamphetamine in sweat by EIA and GC-MS.

Sweat was collected with the PharmChekTM sweat patch and drugs were eluted from the collection pad of the patch. A solid phase, enzyme immunoassay using microtiter plates was modified for analysis of methamphetamine in sweat. After methamphetamine administration, sweat contains primarily parent methamphetamine. The immunoassay was determined to have crossreactivity relative to 100% for the methamphetamine (MA) calibrators; to 144% for methylenedioxymethamphetamine (MDMA); to 30% for d-amphetamine; to 21% for methylenedioxyamphetamine (MDA); and to 8% for I-methamphetamine. The optimum cutoff concentration for this modified assay was determined by receiver operating characteristic analysis to be 10 ng/mL amphetamine equivalents. At this cutoff concentration the assay had a diagnostic sensitivity of 84.5% and a diagnostic specificity of 93.2% versus gas chromatography-mass spectrometry (GC-MS). The positive predictive value at a prevalence of 50% was 86%. The intra-assay precision at 10 ng/mL was 9.9% (coefficient of variation, CV) and the interassay CV was 13%. Analysis of spiked patches at plus or minus 25 and 50% around the cutoff gave a percent positive threshold of approximately 50% at a cutoff of 10 ng/mL and a 95% confidence level for a positive result by the EIA between 15 and 20 ng/mL. Of 18 potential adulterants that might be injected into or under the patch, two (tile cleaner and cough syrup) caused a false-positive response by immunoassay. All results were confirmed by GC-MS. The clinical sensitivity and specificity of the overall analysis system (sweat collection and analysis) were 85 and 100%, respectively, using known methamphetamine dosing of volunteers (10, 20, and 25 mg) as the reference standard.

Sweat Testing for Benzodiazepines

Thirteen subjects participated in a clinical study to determine the cumulative excretion, the time course, the dose-concentration relationship, and concentrations of diazepam in sweat following oral administration of single dose of the drug. Nordiazepam and oxazepam, two metabolites of diazepam, were also investigated. Sweat was collected by means of Sudormed sweat patch. Patches were removed at specified times over one week and drug content was determined by gas chromatography/mass spectrometry (GC/MS) in negative chemical ionization mode using deuterated internal standards. Irrespective of the time of collection, diazepam and nordiazepam were present, but oxazepam was never detected. Drugs were detectable in the 2 to 4-h period following the administration. Peaks of diazepam were obtained during the 48 to 72-h period. After the peak, a decrease of drug concentration was observed. Concentrations were in the range from 0.1 to 6.0 ng/patch for both drugs. After single administration of diazepam (10, 20, or 30 mg), drugs monitored in three groups of three subjects were suggestive to be dose related. All these data suggest that the sweat patch technology can be useful to document drug use over a week-long period of surveillance.