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SOFT 2004 Meeting Abstracts - Society of Forensic Toxicologists

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M29 <br />

CODEINE AND METABOLITE DISPOSITION IN HUMAN SWEAT FOLLOWING<br />

CONTROLLED ORAL CODEINE ADMINISTRATION<br />

Eugene W. Schwilke 1 *, Sherri L. Kacinkol, Allan J. Barnesl, Jonathan M. Oyler2, Edward 1. Cone 3 , Eric T.<br />

Moolchan l , and Marilyn A. Huestis l : IChemistry and Drug Metabolism Section, Intramural Research<br />

Program, NIDA, NIH, Baltimore, MD, 2Department <strong>of</strong> the Army, US Army Research, Development and<br />

Engineering Command, Aberdeen Proving Ground, MD, 3ConeChem Research, LLC., Severna Park, MD<br />

Analysis <strong>of</strong> codeine is included in drug treatment, military, criminal justice and workplace programs<br />

because <strong>of</strong> its abuse potential and performance impairing effects. Interest in monitoring drug exposure with<br />

human sweat, as an alternative biological specimen is increasing, as sweat collections are convenient, less<br />

invasive and difficult to adulterate. Our objective for this study was to determine the excretion pr<strong>of</strong>ile <strong>of</strong><br />

codeine and metabolites into human sweat using the PharmChek Sweat Patch. Volunteers with a history<br />

<strong>of</strong> opiate use (n=9) provided informed consent to participate in this IRB-approved study and resided on the<br />

closed clinical research ward for 12 weeks. Low (60mg/70kg) and high (l20mg/70kg) doses <strong>of</strong> codeine<br />

sulphate were administered three times a week, four weeks apart. Codeine, norcodeine, morphine,<br />

normorphine, and 6-monoacetylmorphine were isolated by SPE and GCIEI-MS. The limit <strong>of</strong> quantitation<br />

(LOQ) for codeine and morphine were 2.5 ng/patch, and 5 ng/patch for metabolites.<br />

We present data from patches representing four categories <strong>of</strong> sweat collection. First, weekly sweat patches<br />

were collected from the time <strong>of</strong> entry onto the secure ward until the time <strong>of</strong> first codeine administration,<br />

reflecting excretion <strong>of</strong> previously self-administered opiates. No patch was positive for 6-acetylmorphine,<br />

codeine, morphine or metabolites at the methods' LOQs.<br />

Second, weekly sweat patches also were applied prior to and removed 7 days after dosing for 5 <strong>of</strong> 9 and 3<br />

<strong>of</strong> 6 participants for the low and high doses, respectively. 80% <strong>of</strong> the low and 100% <strong>of</strong> the high dose<br />

weekly patches were positive for codeine, but negative for metabolites. The mean codeine concentration for<br />

these patches was 65 ng/patch (median 27, SD 92, range 16-225) for the low dose and 82 ng/patch (median<br />

84, SD 15, range 67-96) for the high dose.<br />

Third, other sweat patches were worn for between 1 to 15 hours during the first 48 hours after dosing. Of<br />

139 patches worn during the first 48 hours following the first codeine administration, only 11 (8%)<br />

contained codeine levels greater than our LOQ. Codeine was the only analyte detected and could be found<br />

as early as 1 hour after dosing. A total <strong>of</strong>7 patches (8%) were positive for codeine following the low dose,<br />

and 4 patches (8%) following the high dose. The mean codeine concentration (data from 3 <strong>of</strong>9 subjects) in<br />

sweat was 43 ng/patch (median 28, SD 50, range 5 - 153) for the low dose and 12 ng/patch (median 11.0,<br />

SD 9.0, range 3-24, data from 3 <strong>of</strong> 6 subjects) for the high dose. Codeine was detected in sweat patches for<br />

up to 26 h after administration; patches applied after 26 hours and worn for up to 15 hours were below the<br />

LOQ.<br />

Fourth, weekly patches also were applied to 4 <strong>of</strong> 9 participants two weeks after the last codeine dose. All<br />

<strong>of</strong> the patches also were negative for codeine and metabolites.<br />

Sweat has recently been proposed by the Substance Abuse and Mental Health Services Administration<br />

(SAMHSA) for federally-mandated workplace drug testing. A confirmation cut<strong>of</strong>f <strong>of</strong> 25 ng/patch has been<br />

proposed for patches worn 7 to 14 days. Two patches for one subject and I patch for another collected<br />

within the first 48 hours following dosing, would be positive using these criteria. In comparison, 6 <strong>of</strong> 8<br />

patches worn for 7 days during the dosing period would be positive under the new SAMHSA guidelines.<br />

Sweat provides an adequate matrix for detection <strong>of</strong> opioid use. There was large intra- and inter-subject<br />

variability. No correlation <strong>of</strong> codeine concentration with dose was found for the doses investigated.<br />

Patches worn for 1 week were more likely to contain codeine above the LOQ than patches worn for 1 to 15<br />

hours.<br />

Keywords: Sweat, Codeine, GCMS<br />

Page 312

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