Can Drugs Be Transferred Through The Skin
Clin Chem. Author manuscript; available in PMC 2009 Jul 23.
Published in last edited grade as:
PMCID: PMC2714868
NIHMSID: NIHMS118575
Excretion of Methamphetamine and Amphetamine in Homo Sweat Following Controlled Oral Methamphetamine Administration
Allan J. Barnes
oneChemical science and Drug Metabolism, Intramural Enquiry Programme, National Institute on Drug Abuse, National Institutes of Wellness, Baltimore, Medico
Michael L. Smith
2Sectionalization of Forensic Toxicology, Part of the Armed Forces Medical Examiner, War machine Constitute of Pathology, Rockville, MD
Sherri L. Kacinko
1Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Md
Eugene W. Schwilke
1Chemistry and Drug Metabolism, Intramural Research Programme, National Institute on Drug Corruption, National Institutes of Health, Baltimore, Doctor
Edward J. Cone
threeJohns Hopkins Schoolhouse of Medicine, Baltimore, Physician.
Eric T. Moolchan
1Chemistry and Drug Metabolism, Intramural Inquiry Program, National Found on Drug Corruption, National Institutes of Wellness, Baltimore, Medico
Marilyn A. Huestis
aneChemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Corruption, National Institutes of Health, Baltimore, Physician
Abstract
BACKGROUND
Understanding methamphetamine (MAMP) and amphetamine (AMP) excretion in sweat is of import for interpreting sweat and pilus testing results in judicial, workplace, and drug handling settings.
METHODS
Participants (n = viii) received 4 10-mg (depression) oral doses of sustained-release South-(+)-MAMP HCl (d-MAMP HCl) inside i calendar week in a double-blind, institutional review board–approved written report. Five participants besides received iv xx-mg (high) doses 3 weeks later. PharmChek sweat patches (n = 682) were worn for periods of 2 h to ane week during and up to 3 weeks later on dosing. The mass of MAMP and AMP in each patch was measured past GC-MS, with a limit of quantification of 2.5 ng/patch.
RESULTS
MAMP was measurable in sweat inside 2 h of dosing. After low and high doses, 92.9% and 62.v% of weekly sweat patches were positive, with a median (range) MAMP of 63.0 (16.8 – 175) and 307 (199 – 607) ng MAMP/patch, respectively; AMP values were 15.5 (6.five – 40.five) and 53.8 (34.0 – 83.4) ng AMP/patch. Patches applied 2 weeks after the drug administration week had no measurable MAMP post-obit the low doses, and only 1 positive result following the high doses. Using criteria proposed past the Substance Abuse Mental Health Services Administration, 85.7% (low) and 62.5% (high) weekly sweat patches from the dosing week were positive for MAMP, and all patches applied after the dosing week were negative.
CONCLUSIONS
These data characterize the excretion of MAMP and AMP later controlled MAMP administration and provide a framework for interpretation of MAMP sweat test results in clinical and forensic settings.
Methamphetamine (MAMP)4 abuse in the US continues to increase (1), with more MAMP-related arrests and a higher number of treatment admissions. Routes of administration include intravenous, insufflation, smoking, and oral. Recent reports have described an oral ingestion technique called "parachuting," in which a swallowed tissue containing MAMP unfolds for fourth dimension-released doses (two). Criminal justice and treatment programs detect prohibited drug employ with sweat, pilus, oral fluid, and/or urine testing (3–6). Understanding the excretion of MAMP and its metabolite amphetamine (AMP) in sweat is of import for interpreting results of sweat and hair monitoring methods. The importance of pilus testing derives from transfer of MAMP in sweat to pilus (7).
Sweat testing is conducted using patches cleared for utilize by the Food and Drug Administration, which are usually worn for 1 week (viii, nine). Patches provide a qualitative tape of an individual's drug use over the period of ascertainment. Sweat patches are a less invasive ways of specimen collection than blood testing and circumvent the privacy problems of urine collection. Disadvantages are the possibility of time-dependent drug loss from the patch by drug degradation on the patch or skin, reabsorption into the skin, and volatile losses through the roofing membrane of the patch (10). There also are reports of patch contamination by cocaine, heroin, or MAMP remaining on the skin before patch application (xi). Despite these limitations, sweat testing can exist useful if appropriate wash procedures are used before application, and patch removal is properly timed. A number of investigators have reported clinical study results for opiates (iv, 12, 13), cocaine (viii, 9, fourteen–17), MAMP (18), and 3,4-methylenedioxymethamphetamine (MDMA) (xix).
There have been no well-controlled studies of the excretion of MAMP or AMP into sweat. In an early on study, investigators administered South-(+)-dimethylamphetamine to 2 individuals and collected sweat after physical exertion (20). They reported that the parent drug and its metabolite MAMP appeared in sweat as early as 1.5 h. Using immunoassay and GC-MS, Fay et al. (18) analyzed weekly sweat patches from known MAMP users and individuals given MAMP. The written report was designed to validate the analytical method and did not fully depict the individuals or their drug use history. Pichini et al. (nineteen) administered a single oral dose of 100 mg MDMA, a congener of MAMP, to nine individuals and found that the parent drug appeared in sweat after ane.v h and peaked at 24 h. The betwixt-individual mass of MDMA varied from 3.2 to 1326 ng/patch. The metabolite three,4-methylenedioxyamphetamine (MDA) was present in trace amounts in the sweat of 7 of ix individuals.
In this comprehensive double-bullheaded, placebo-controlled, multiple-dose study, we examined sweat collected from eight individuals before, during, and after daily oral administration of 4 low (ten mg) and loftier (20 mg) doses of sustained-release MAMP administered within 7 days. Times of 1st detection, top and duration of excretion, and expected mass/patch of MAMP and AMP in sweat were measured past GC-MS. Information were analyzed using the limit of quantification (LOQ) of 2.five ng/patch and the Substance Abuse and Mental Health Services Administration (SAMHSA) proposed guidelines for MAMP and AMP sweat testing (three). These proposed guidelines plant a confirmation cutoff of 25 ng/patch for each compound, with an boosted requirement forAMPto be present at or above the method's limit of detection to study a positive MAMP result.
Materials and Methods
PARTICIPANTS AND DRUG ADMINISTRATION
Four male (ii Hispanic, two not-Hispanic white; ages 26 – 39 years; weight 61.5–106.5 kg) and four female (4 African Americans, ages 34 – 43 years; weight 56.6 – 75 kg) volunteers provided informed consent and were financially compensated for their time and effort during participation in this investigation, which was canonical by the National Institute on Drug Abuse Institutional Review Board. Before admission, individuals with a history of stimulant and opioid use underwent thorough medical (physical exam, electrocardiography, and claret and urine chemistries) and psychological evaluations. For the duration of the study (x weeks), participants resided on the secure clinical inquiry unit, under 24-h medical surveillance, to ensure condom and to prevent additional drug utilise. The participants were free to deport normal activities, including practice in the air-conditioned facility and basketball and volleyball outside in a walled courtyard. The written report was conducted over multiple years at all seasons of the twelvemonth.
The 1st ii weeks of the study served as a washout period to permit emptying of previously self-administered drugs. In the 3rd week, participants (n = 8) received four daily sustained-release doses of 10 mg (low) oral S-(+)-methamphetamine HCl (d-methamphetamine HCl) within a 7-day menstruation (see Fig. 1). The study design included four consecutive daily doses; however, some administrations were non on consecutive days considering of either increased baseline heart rate or research unit schedules, but all were within 7 days. After at to the lowest degree a iii-week interval that included administration of placebo, v of 8 participants also received iv daily 20 mg (high) oral doses. Two participants were butterfingers for medical reasons and a 3rd for personal problems. Participants were administered a single capsule containing ane or 2 Desoxyn Gradumet 10-mg sustained-release tablets (Abbott Laboratories) with lactose (Amend Drug & Chemical Co., Inc.) as the filler. This conception was developed to sustain tedious release of drug later oral assistants. For placebo treatments, the sheathing contained but lactose filler. Boosted information about the participants and administered drug and simultaneously obtained plasma, oral fluid, and urine information may be found in previous publications (21–23).
Methamphetamine administration schedule for 4 10-mg (depression) and 4 xx-mg (loftier) oral MAMP doses
Washout refers to the 2 weeks earlier drug administration that permitted excretion of previously self-administered illicit drugs. P1, P2, and P3 refer to the 1st, 2nd, and 3rd weeks later on the low and high doses to monitor balance drug excretion after the dosing week.
SWEAT Collection
Weekly sweat patches
PharmChek® (PharmChem Inc.) sweat patches were practical to participants upon access, ane on the dorsum and 1 on the abdomen, and removed at the end of 1 week. Indistinguishable patches also were practical in the same manner every calendar week for the elapsing of the protocol (x weeks). The sweat patch device consists of an adhesive layer on a sparse transparent picture show of surgical dressing and a rectangular, absorbent, cellulose pad (xiv cm2). The surgical dressing picture allows oxygen, carbon dioxide, and water vapor to escape while the nonvolatile constituents in sweat are retained in the absorbent pad. Patches practical and removed in the 1st 2 weeks before dosing were termed washout patches. Dosing patches were applied earlier the 1st dose and removed up to 7 days afterward. Weekly patches applied afterward the end of drug administration were defined equally postdose patches. Data for indistinguishable patches were reported individually, and median values were determined using all information, not using mean data for the replicates. 5 (0.6%) of the 786 sweat patches did non adhere throughout the wear period. Unacceptable data were obtained for 3 patches (0.iv%) owing to the lack of addition of internal standard. 19 patches (2.4%) were not practical owing to clinical or administration issues, and 28 (three.vi%) were removed because of peel irritation. The most regrettable was the loss of 48 short-term and 20 weekly patches between collection and analysis. Further detail (whether the loss occurred during brusk- or long-term storage on the research unit) is unavailable.
SHORT-TERM SWEAT PATCHES
Single patches were applied to monitor excretion throughout each day that drug was administered (Fig. ii). The patches after the 1st dose covered the time periods 0–2 h, 2–4 h, 4–8 h, 8–23 h (15-h patch), and 23–24 h (baseline patch for the next mean solar day'south dosing). On subsequent dosing days, brusque-term sweat patches covered the periods of 0–ix h and 9–24 h (15-h patch).
Short-term sweat patch awarding and removal schedule
Short-term sweat patches were applied for 0–two, 2–4, 4–viii, 8–23, and 23–24 h after the kickoff depression- and loftier-dose methamphetamine assistants, and 0–9 and 9–24 h for the other iii dosing days.
The skin was thoroughly cleaned with an isopropyl alcohol prep wipe (70% vol/vol) before patch awarding. Later removal, patches were placed into plastic specimen bags along with a clean index menu with identification information, sealed, and stored at −20 °C until analysis.
REAGENTS AND MATERIALS
We purchased MAMP, AMP,MAMP-d11, and AMP-dten from Cerilliant; N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) with one% trimethylchlorosilane (TMCS) and Northward-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA) with 1% tert-butyldimethylchlorosilane (TBDMCS) from Pierce Chemic; and filtration columns (RFV02F4P) and solid-phase extraction (SPE) columns (Clean Screen CSDAU020) from United Chemical Technologies.
GC/MS Assay
We analyzed sweat patches for MAMP and AMP by modification of a published SPE GC/MS procedure (14, 24). These modifications permitted simultaneous quantification of MAMP, AMP, opiates, cocaine, and metabolites in a single analysis. Briefly, nosotros added calibrators and control solutions to drug-free patches and added deuterated internal standards directly to calibrator, command, and participants' sweat patches. Patches were folded and placed into 12-mL filtration columns fitted with stopcocks. A 4-mL aliquot of 0.v mol/50 sodium acetate buffer (pH four.0) was added, and the sweat patch remained immersed in this solution for 30 min at room temperature. We collected buffered eluates in disposable sixteen by 100mm drinking glass test tubes. This step was repeated twice using 2 mL buffer and 30-min immersion intervals. Nosotros practical the combined buffered extracts (8 mL) to SPE columns preconditioned with ane mL freshly prepared elution solvent; methylene chloride: 2-propanol:ammonium hydroxide (80:20:2, vol/vol/vol), methanol (1 mL), distilled water (3 mL), and one.v mL of 2.0 mol/L sodium acetate buffer (pH iv.0). The columns were washed with distilled h2o (3 mL), 0.2 mol/L muriatic acid (ane.five mL), and methanol (three mL) and dried for 5min under total vacuum. Analytes of interest were eluted using 5 aliquots (i mL) of elution solvent. Nosotros added 20 µL MTBSTFA with 1% TBD MCS to each tube to reduce MAMP and AMP volatility (24) and evaporated the eluates to dryness under nitrogen. Extracts were reconstituted in acetonitrile and subjected to dual derivatization with MTBSTFA with 1% TBDMCS and BSTFA with 1% TMCS. Derivatives were analyzed in splitless way on an Agilent 6890 gas chromatograph/5973 quadrupole mass selective detector operated in electron ionization mode. The temperatures of the quadrupole, ion source, and mass selective detector interface were 150, 250, and 295 °C, respectively. The injection port temperature was maintained at 250 °C. The initial oven temperature was maintained at 70 °C for 1 min, followed past ramps of 30 °C/min to 175 °C, 23 °C/min to 250 °C, and eighteen °C/min to a final temperature of 310 °C, which was held for 3 min.
In each analytical run, we synthetic ii calibration curves for each analyte to establish extended calibration ranges. Depression (ii.5–50 ng/patch) and high (50–500 ng/patch) calibration curves (n = 10) were constructed for MAMP and AMP, with coefficients of conclusion (R2) ≥0.989. LOQs for MAMP and AMP were 2.five ng/patch. We calculated estimates of imprecision using duplicate controls from ten analytical runs (n = 20) according to Krouwer and Rabinowitz (25). For all runs, the pooled within-run component of imprecision, expressed equally %CV, was < 12.4% for all control concentrations (iii.75, 12.5, 125, and 375 ng/patch). Between-run imprecision (%CV) for all analytes, at all concentrations, was <12.1% for methamphetamine and <10.half dozen% for amphetamine. Full imprecision of the method (%CV) was reported equally <17.8% and <xx.8% for MAMP and AMP, respectively. Recoveries were inside 10.2% of target concentrations.
Results
We collected 682 sweat patches from viii participants throughout the 10-week study. No weekly patch (due north = 38) collected during the washout period had detectable MAMP or AMP. After controlled administration of 40 and fourscore mg sustained-release MAMP (4 10- or xx-mg doses inside 1 week), parent drug was the master analyte detected in sweat. With the exception of half dozen brusque-term patches, AMP was also detected in all patches with MAMP values >25 ng/patch. In addition, x patches (ane.5%) contained AMP in a higher place the method LOQ without concurrent MAMP; 5 of these were weekly patches.
MAMP was the only analyte detected in whatsoever short-term patch (due north = 32) worn at intervals (0 –2, two–4, 4–8, 8–23 h) after the first low-dose administration (Tabular array 1). Twelve of these short-term patches (37.5%) had MAMP to a higher place the LOQ. Because of the absence of AMP, no patch met the SAMHSA criteria for a positive result. Afterwards the first 20-mg MAMP assistants, 75% of brusque-term sweat patches (northward = 16) were positive for MAMP above the assay LOQ and 25% satisfied SAMHSA requirements for a positive specimen. MAMP was 1st detected in short-term sweat patches practical merely before dosing and removed 2 h afterwards (0–2 h). AMP was detected in short-term patches only after the high dose (Table 1).
Table 1
Methamphetamine and amphetamine results for hourly (2, 4, and 15 h) patches worn during or afterward a single depression-dose (10 mg) or high-dose (20 mg) oral MAMP assistants.
| Time after dose, h | Time worn, h | MAMP ≥LOQ, northa | Median MAMP, ng/patch (range) | AMP ≥LOQ, na | Median AMP, ng/patch (range) | ≥SAMHSA, nb |
|---|---|---|---|---|---|---|
| Depression dose (north =eight) | ||||||
| 0–2 | two | i | 4.8 | 0 | Not detectedc | 0 |
| ii–four | 2 | 1 | three.ane | 0 | Not detectedc | 0 |
| iv–8 | 4 | 5 | five.viii (iii.0–23.3) | 0 | Not detectedc | 0 |
| viii–23 | 15 | 5 | xi.2 (five.3–42.3) | 0 | Not detectedc | 0 |
| High dose ( n = 5) | ||||||
| 0–2 | 2 | 2 | 46.5 (half dozen.9–86.0) | 1 | xviii.6 | 1 |
| 2–iv | 2 | three | 9.8 (6.1–21.iv) | 0 | Non detectedc | 0 |
| four–8 | iv | 3 | 34.2 (33.1–41.4) | one | 4.4 | 1 |
| 8–23 | 15 | 4 | 28.3 (xviii.nine–103.4) | iii | v.0 (3.three–8.4) | 2 |
Results for 15-h patches worn at the stop of each day of MAMP administration are presented in Table 2. Later 4 low and high doses, respectively, 67.7% of patches (due north = 31) and 92.9% of patches (n = 14) were to a higher place the LOQ for MAMP, vs 25.eight% and 78.6% for AMP. Five of 31 15-h patches later on low MAMP doses were positive by SAMHSA guidelines, vs vii of xiv afterwards high doses. AMP was only present without MAMP in 2 of 49 patches, and never at ≥25 ng/patch to fulfill SAMHSA requirements for a positive AMP sweat test.
Table 2
Methamphetamine and amphetamine mass per sweat patch worn for xv h at the end of each mean solar day afterwards administration of 4 daily low (10 mg) or loftier (xx mg) MAMP doses.
| MAMP | AMP | MAMP | AMP | MAMP | AMP | MAMP | AMP | |
|---|---|---|---|---|---|---|---|---|
| Low dose | ||||||||
| northward | eight | eight | seven | 7 | eight | 8 | 8 | 8 |
| ≥LOQ, na | 5 | 0 | 5 | three | 5 | 2 | 6 | 3 |
| Median ng/patch (range) | 11.two (5.three–42.three) | ND | 32.5 (v.0–82.1) | ix.5 (ii.ix–9.viii) | v.ix (2.8–72.4) | 10.2 (8.0–12.4) | 23.7 (16.eight–104) | 4.8 (ii.8–twenty.1) |
| ≥25 ng/patch, due north | 1 | 0 | iii | 0 | 1 | 0 | iii | 0 |
| ≥SAMHSA, nb | 0 | 0 | 2 | 0 | 1 | 0 | 2 | 0 |
| High dose | ||||||||
| n | iv | iv | 4 | 4 | 3 | iii | 3 | 3 |
| ≥LOQ, na | 4 | iii | 3 | 3 | three | 3 | iii | 2 |
| Median ng/patch (range) | 28.iii (xviii.9–103) | five (3.3–8.4) | 70.half-dozen (22.7–215) | fifteen.8 (5.1–21.v) | 68.5 (15.8–148) | 8.five (3.nine–19.4) | 17.1 (11.5–74.8) | 8.one (5.ii–11.0) |
| ≥25 ng/patch, north | two | 0 | ii | 0 | 2 | 0 | 1 | 0 |
| ≥SAMHSA, northwardb | 2 | 0 | 2 | 0 | 2 | 0 | 1 | 0 |
Weekly patches were worn during the 40- and 80-mg cumulative MAMP dosing week. During the low dose, 13 of fourteen weekly patches had MAMP above the LOQ, with a median (range) for positive patches of 63.0 (16.8 – 175) ng/patch. All of these patches were positive for AMP, with a median mass/patch of 15.v (6.v–40.five) ng/patch (Table 3). Twelve of 14 were positive for MAMP by SAMHSA criteria. During the cumulative 80-mg assistants menses, 5 of 8 weekly patches were above the assay'south LOQ for MAMP, with six of 8 positive for AMP. For positive weekly sweat patches, the median (range) mass/patch values were 307 (199–607) ng/patch and 53.8 (34.0–83.iv) ng/patch for MAMP and AMP, respectively. All MAMP-positive weekly sweat patches worn during the high-dose status also contained AMP above the SAMHSA cutoff of 25 ng/patch, and 1 of 8 weekly patches contained AMP without concurrent MAMP. A larger percentage of weekly patches (85.7%) were positive by SAMHSA criteria during the low compared to the high doses (62.5%). However, this was non statistically significant using χ2 analysis (P > 0.05), potentially owing to the pocket-size number of patches or to the differences in MAMP sweat excretion in the individuals receiving the low and loftier doses. For the weeks subsequently either the low or high dosing week, there were no positive sweat patches when applying SAMHSA criteria (Tabular array 3). The week afterward the low-dose week (northward = 13), 61.5% and 30.8% of patches were above the LOQ for MAMP and AMP, respectively. Both analytes were below the LOQ for all weekly patches collected 2 and 3 weeks after low dose. Note that many of the missing information points were for weeks that followed a week when patches were negative at the LOQ. One would expect these patches to as well exist negative. Detection rates increased after the loftier doses. In the week after the loftier MAMP doses (due north = 7), 100.0% (MAMP) and 71.four% (AMP) of patches exceeded the LOQ. In the same individuals, when using a 2.5µg/L urinary cutoff (LOQ), Oyler et al. (23) reported last detection times up to 169 h from the last MAMP dose. Our results testify positive sweat patches during this time frame (after dose week 1). In addition, i weekly patch collected in week ii after high dose contained MAMP(15.ii ng). There were no positive urine tests at this time. All other week 2 and week iii postdose patches had no detectable drug. There were no positive sweat patches with the proposed federally mandated cutoffs. Of course it is not expected that drug test results will be identical betwixt matrices due to unlike analytes and analytical cutoffs, dissimilar periods of time for drove—i.eastward., sweat patches accumulate drug over ane week vs a unmarried urine sample representing only a few hours of excretion (26).
Table 3
Mass of MAMP and AMP in weekly sweat patches during (week 1) and after administration of four ten-mg (low) or 4 xx-mg (high) doses of MAMP within 1 week.
| Bailiwick | During Week 1 MAMP | AMP | Subsequently Week 1 MAMP | AMP | Week 2 MAMP | AMP | Week 3 MAMP | AMP |
|---|---|---|---|---|---|---|---|---|
| Low dose | ||||||||
| ane | 56.9 | 21.0 | 22.9 | 13.7 | <ii.5 | <2.5 | <2.5 | <2.5 |
| one | a | a | <2.v | <ii.v | a | a | a | a |
| 2 | 175 | 40.5 | a | a | a | a | a | a |
| 2 | 121 | 21.vii | a | a | a | a | a | a |
| 3 | 73.2 | 32.five | <2.5 | <2.v | <two.5 | <2.5 | a | a |
| iii | 58.3 | 27.3 | <2.5 | <two.v | <2.5 | <2.5 | a | a |
| 4 | 16.8 | 6.5 | <ii.five | <ii.5 | a | a | a | a |
| 5 | 38.two | 7.1 | 4.2 | <2.five | <2.5 | <two.v | a | a |
| 5 | 28.3 | eight.half-dozen | 4.2 | <2.5 | <2.v | <two.v | a | a |
| 6 | 44.9 | 7.6 | <two.five | <two.5 | <2.five | <ii.v | <ii.5 | <ii.5 |
| vi | 63.0 | 10.9 | 8.2 | ii.6 | <2.5 | <2.5 | <2.5 | <2.v |
| 7 | 130 | 15.9 | nine.9 | 2.6 | <two.5 | <2.5 | a | a |
| 7 | 115 | 15.0 | eight.7 | 2.five | <2.5 | <2.5 | a | a |
| 8 | <2.5 | 16.1 | 4.3 | <2.five | <ii.5 | <2.5 | a | a |
| 8 | 72.9 | 13.iii | 5.0 | <ii.5 | <2.5 | <2.five | a | a |
| ≥LOQb | xiii | 14 | eight | 4 | 0 | 0 | 0 | 0 |
| ≥SAMHSAc | 12 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Total | 14 | 14 | xiii | 13 | xi | 11 | iii | 3 |
| Median | 63.0 | 15.v | five.0 | two.6 | ||||
| Minimum | xvi.eight | 6.five | four.2 | 2.5 | ||||
| Maximum | 175 | 40.5 | 22.9 | xiii.seven | ||||
| High dose | ||||||||
| ane | 199 | 34.0 | 24.nine | 14.2 | 15.2 | <two.5 | <2.5 | <two.five |
| iii | 306 | 83.4 | vii.eight | 3.7 | <2.five | <two.five | a | a |
| iii | 303 | 82.3 | four.4 | 2.nine | <2.v | <2.5 | a | a |
| 5 | <2.5 | <2.5 | iii.8 | <2.five | a | a | a | a |
| 5 | <2.5 | <ii.v | 2.8 | <2.5 | a | a | a | a |
| seven | 607 | 66.vi | 12.4 | iv.0 | <ii.v | <2.5 | <2.five | <2.5 |
| 7 | 322 | xl.9 | eleven.v | 3.viii | <2.five | <2.5 | <2.5 | <2.v |
| eight | <ii.five | twoscore.ix | a | a | <two.5 | <2.5 | a | a |
| eight | a | a | a | a | <2.5 | <2.5 | a | a |
| ≥LOQb | five | 6 | vii | 5 | 1 | 0 | 0 | 0 |
| ≥SAMHSAc | 5 | vi | 0 | 0 | 0 | 0 | 0 | 0 |
| Total | 8 | 8 | seven | 7 | 7 | seven | 3 | iii |
| Median | 307 | 53.eight | vii.eight | 3.8 | 0.0 | |||
| Minimum | 199 | 34.0 | 2.8 | 2.9 | fifteen.2 | |||
| Maximum | 607 | 83.four | 24.nine | 14.2 | 15.two | |||
Tabular array 4 compares the cumulative mass/patch of MAMP and AMP in short-term patches to comparable weekly patches. For 9 of 12 dosing occasions, the cumulative mass/patch was greater than the average weekly mass/patch of MAMP. Some differences were large, with cumulative mass/patch more than than twice that of the average weekly patches. Differences for AMP betwixt cumulative short-term and weekly patches were less frequent and of smaller magnitude.
Tabular array 4
Comparison of MAMP and AMP mass per patch in duplicate weekly sweat patches with corresponding cumulative mass per patch in hourly patches covering the same MAMP assistants period.
| Methamphetamine, ng/patch | Amphetamine, ng/patch | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| | | |||||||||
| Subject | Weekly patch 1 | Weekly patch two | Mean | Hourly sum | Difference | Weekly patch 1 | Weekly patch 2 | Hateful | Hourly sum | Deviation |
| Low dose | ||||||||||
| | ||||||||||
| i | 56.9 | — | — | 69.6 | 12.seven | 21.0 | — | — | 6.5 | −14.5 |
| | ||||||||||
| 2 | 175 | 121 | 148 | 431 | 283 | xl.v | 21.7 | 31.one | 64.9 | 24.4 |
| | ||||||||||
| iii | 73.2 | 58.3 | 65.8 | 103 | 36.eight | 32.5 | 27.3 | 29.nine | 38.8 | 6.3 |
| | ||||||||||
| iv | 16.eight | — | — | 11.2 | −v.6 | 6.5 | — | — | 0.0 | −6.v |
| | ||||||||||
| 5 | 38.2 | 28.3 | 33.3 | 27.1 | −6.2 | vii.1 | 8.6 | seven.ix | 0.0 | −7.i |
| | ||||||||||
| 6 | 44.9 | 63.0 | 54.0 | 73.two | nineteen.iii | 7.6 | 10.9 | ix.3 | 0.0 | −vii.6 |
| | ||||||||||
| 7 | 131 | 115 | 123 | 207 | 83.8 | xv.9 | 15.0 | 15.5 | sixteen.0 | 0.i |
| | ||||||||||
| 8 | 0.0 | 72.9 | 36.five | 102 | 66.0 | 16.ane | 13.3 | 14.7 | 10.4 | −five.7 |
| | ||||||||||
| High dose | ||||||||||
| | ||||||||||
| i | 199 | — | — | 250 | 50.viii | 34.0 | — | — | 19.8 | −fourteen.2 |
| | ||||||||||
| 3 | 307 | 303 | 305 | 149 | −156 | 83.iv | 82.three | 82.9 | 189 | 106 |
| | ||||||||||
| 5 | 0.0 | 0.0 | 0.0 | 229 | 229 | 0.0 | 0.0 | 0.0 | 42.4 | 42.iv |
| | ||||||||||
| seven | 607 | 322 | 465 | 1106 | 641 | 66.6 | twoscore.9 | 53.8 | 133 | 66.1 |
Discussion
This comprehensive, controlled, multiple oral dose MAMP assistants study addressed the disposition of MAMP and its metabolite AMP in human sweat. The written report was conducted on a closed inquiry unit of measurement, and included a ii-week washout menstruum to ensure that drug detected was not from prior self-administration. Sweat patches (n = 682) were applied and removed at various times to monitor excretion of drug into sweat during hourly and weekly timeframes. MAMP was the principal analyte identified after MAMP administration. This besides was reported by Fay et al. (18), also as a review of the clinical pharmacokinetics of amphetamines (27). MAMP in our written report appeared equally early on as 2 h later on oral dosing, consistent with the findings of Vree et al. (20), who reported the appearance of parent drug in sweat in 2 participants 1.v h later on oral administration of twenty mg S-(+)-dimethylamphetamine. Pichini et al. (19) observed the advent of MDMA in sweat 1.5 h after administration and demonstrated high interindividual variability in mass MDMA/patch values in weekly patches, consistent with our findings of weekly MAMP mass/patch from <2.v to 175 ng/patch during administration of xl mg MAMP, and <2.five to 607 ng/patch for fourscore mg MAMP. Some variability is explained by different sweat excretion rates (10) and differences in bioavailability and metabolism betwixt individuals. Other possibilities are loss of drug through degradation on the patch or pare, reabsorption through the skin, and potential loss through the outer sweat patch covering to the environment. We found that for most drug administration occasions, cumulative short-term mass MAMP/patch values were greater than the weekly mass MAMP/patch values roofing the same periods (Table 4). This could indicate that in that location was some loss of MAMP from the patches worn for 1 week through the mechanisms discussed by Uemura et al. (10). This group found that deuterated cocaine placed on sweat patches could exist captivated through skin over a period of fourth dimension. They also observed up to 8-fold differences in mass cocaine/patch with patch location. We did not observe these differences for MAMP on sweat patches placed on the back and abdomen. Loss from patches did not appear to be meaning for AMP.
Mass MAMP/sweat patch values were college on the 2nd solar day of administration, but median mass/patch did non continue to increase on subsequent dosing days. This besides was truthful for mass MAMP/sweat patch in the subset of patches worn the final 15 h of each dosing day. These sweat patches showed that the median mass MAMP/patch was greater for the college doses, only the number of patches positive using an LOQ cutoff or SAMHSA criteria were not significantly different between doses.
AMP did non appear in measurable amounts in sweat the 1st 24-hour interval afterward a 10-mg dose of MAMP, but was excreted within the outset 2 h for 1 individual after the 20-mg dose. Vree et al. (20) found that the metabolite S-(+)-methylamphetamine, later a 20-mg oral dose of Due south(+)-dimethylamphetamine, peaked in 5 and 7 h for 2 participants. One might expect in our study to see the highest mass/patch of the metabolite AMP in this time-frame. AMP also was present in three of iv patches collected the terminal 15 h of the 1st high-dose twenty-four hour period and in amounts that were near ten% of those for MAMP. On days two through 4 of the high-dose administration, AMP was detectable in most brusk-term patches, but was <25 ng/patch.
It is interesting that a larger percent of weekly sweat patches worn during depression drug administration had MAMP above the LOQ for the low (92.9%) vs the loftier (62.5%) dose, despite the median mass MAMP/patch being >four times higher. Using SAMHSA criteria yielded similar positive rates, 85.7% vs 62.v%. The differences are large but not statistically significant given the small sample size (χ2, P > 0.05). These results indicate that, with the recommended cutoff mass/patch, detection rates may vary independent of administered dose.
Our findings have implications for interpreting hair examination results. Contamination of hair past drugs in sweat is well documented (seven, 28–33), and hair-testing laboratories have different methods for removing external contagion (29, 34, 35). Our results demonstrate that MAMP may be nowadays in sweat within two h of oral ingestion and may exist excreted for >1 week afterwards cessation of multiple uses. Information technology is possible for MAMP in sweat to get incorporated into hair during this period of time.
Based on our results, clinicians who wish to monitor individuals in drug treatment programs can wait to detect a cumulative dose of MAMP as modest as 40 mg with a weekly sweat patch. For individuals taking a total dose of 80 mg MAMP, one would expect weekly patches worn during administration to be positive but patches practical in the weeks after drug cessation to exist negative using SAMHSA criteria. These information provide a scientific database for interpreting MAMP and AMP sweat test results and contribute to improved clinical monitoring of MAMP apply.
Acknowledgments
Grant/funding Support: The research was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Wellness, and the American Registry of Pathology. We would also like to give thanks PharmChem for generously providing sweat patches for this study.
Footnotes
4Nonstandard abbreviations: MAMP, methamphetamine; AMP, amphetamine; MDMA, iii,4-methylenedioxymethamphetamine; MDA, 3,4-methylenedioxyamphetamine; LOQ, limit of quantification; SAMHSA, Substance Abuse and Mental Health Services Assistants; BSTFA, N,O-bis(trimethylsilyl)trifluoroacetamide; MTBSTFA, Northward-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide; TBDMCS, tert-butyldimethylchlorosilane; SPE, solid-phase extraction.
Fiscal Disclosures: None declared.
The opinions in this article are those of the authors and practise non necessarily reflect the views of the National Institute on Drug Abuse or the Section of Defense.
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714868/
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