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ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Dose-Related Distribution of Codeine, Cocaine, and Metabolites into Human Hair following Controlled Oral Codeine and Subcutaneous Cocaine Administration

Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (K.B.S., E.T.M., M.A.H.); and ConeChem Research, LLC, Severna Park, Maryland (E.J.C.)

Hair testing for the determination of drug exposure has many useful applications. Drug incorporated into hair can be found for extended periods following drug exposure. There are few controlled drug administration studies investigating drug distribution into human hair. Ten volunteers participated in a 10-week controlled cocaine and codeine administration study while residing in the secure research ward. Weekly hair samples were collected by electric razor. During the low-dose week (week 4), volunteers received 75 mg/70 kg cocaine subcutaneously and 60 mg/70 kg codeine orally on alternating days, a total of three doses for each drug. Similarly, during week 7, volunteers received three doses 150 mg/70 kg cocaine and 120 mg/70 kg codeine. Maximum hair concentrations (C_max) were found 1 to 3 weeks after low and high doses. Dose-related C_max values of cocaine, benzoylecgonine, ecgonine methyl ester, norcocaine, cocaethylene, and codeine were found following low and high doses. Hair analysis was performed using liquid chromatography tandem mass spectrometry. A positive linear relationship was found between total melanin content of hair and C_max of codeine, cocaine, and metabolites following high dosing. This study demonstrated dose-related concentrations of cocaine and metabolites in human hair following controlled cocaine administration. These data are the first demonstrating melanin-related incorporation of cocaine and metabolites into human hair following controlled cocaine administration.

Address correspondence to: Dr. Marilyn A. Huestis, Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Dr., Baltimore, MD 21224. E-mail: mhuestis{at}intra.nida.nih.gov

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