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Research ArticleArticle

The Incorporation of Cocaine and Metabolites into Hair: Effects of Dose and Hair Pigmentation

Deanna L. Hubbard, Diana G. Wilkins and Douglas E. Rollins
Drug Metabolism and Disposition December 2000, 28 (12) 1464-1469;
Deanna L. Hubbard
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Diana G. Wilkins
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Douglas E. Rollins
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Abstract

The relationship between xenobiotic concentrations in hair and the degree of systemic xenobiotic exposure is poorly defined. The purpose of this study was to evaluate the effect of dose, time, and pigment on the hair incorporation of cocaine (COC) and its metabolites, benzoylecgonine (BE), ecgonine methyl ester (EME), and norcocaine (NCOC). COC was administered by the i.p. route to male Long-Evans (LE) rats at three doses (5, 10, and 20 mg/kg) once daily for 5 days. Fourteen days after the initial injection, the hair was collected and analyzed by gas chromatography/mass spectrometry for the compounds of interest. COC, EME, and NCOC were preferentially incorporated into pigmented hair in a dose-dependent manner. None of the analytes were detected in nonpigmented hair. The plasma pharmacokinetic profile of each analyte was determined at each dose. After normalizing for the plasma concentrations, the incorporation of COC into pigmented hair was 2 orders of magnitude greater than BE. The time course of COC and metabolite distribution into hair was also investigated from 1 h to 14 days after a single dose. After COC disappears from plasma, there is a 3-day delay before maximal hair concentrations are reached in pigmented hair. In nonpigmented hair, concentrations of BE and COC did not exceed 0.25 ng/mg and were undetectable after 4 h and 2 days, respectively. This study demonstrates that the pigment-mediated differences in the incorporation of COC and its metabolites noted at 14 days after dosing are also evident a few hours after drug administration.

Footnotes

  • Send reprint requests to: Dr. Douglas E. Rollins, Center for Human Toxicology, University of Utah, 20 S. 2030 E., Rm. 490, Salt Lake City, UT 84112-9457. E-mail: drollins{at}alanine.pharm.utah.edu

  • This research supported by National Institute on Drug Abuse (NIDA) Grant DA-078280.

  • Abbreviations used are::
    PCP
    phencyclidine
    COC
    cocaine
    BE
    bezoylecgonine
    EME
    ecgonine methyl ester
    NCOC
    norcocaine
    SPE
    solid phase extraction
    ICR
    incorporation ratio
    LLOD
    lower limit of detection
    LLOQ
    lower limit of quantitation
    LE
    Long-Evans
    GC/MS
    gas chromatography/mass spectrometry
    • Received June 12, 2000.
    • Accepted August 23, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 28 (12)
Drug Metabolism and Disposition
Vol. 28, Issue 12
1 Dec 2000
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Research ArticleArticle

The Incorporation of Cocaine and Metabolites into Hair: Effects of Dose and Hair Pigmentation

Deanna L. Hubbard, Diana G. Wilkins and Douglas E. Rollins
Drug Metabolism and Disposition December 1, 2000, 28 (12) 1464-1469;

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Research ArticleArticle

The Incorporation of Cocaine and Metabolites into Hair: Effects of Dose and Hair Pigmentation

Deanna L. Hubbard, Diana G. Wilkins and Douglas E. Rollins
Drug Metabolism and Disposition December 1, 2000, 28 (12) 1464-1469;
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