Published: Journal of Analytical Toxicology, ISSN 0146-4760, Volume 30, Number 8, October 2006, pp.501-510

Major and Minor Metabolites of Cocaine in Human Plasma following Controlled Subcutaneous Cocaine Administration
Erin A. Kolbrich[1], Allan J. Barnes[1], David A. Gorelick[2], Susan J. Boyd[3], Edward J. Cone[4], and Marilyn A. Huestis[1],
[1]Chemistry and Drug Metabolism, IRP, NIDA, NIH, 5500 Nathan Shock Drive, Baltimore, Maryland 21224;
[2]Office of the Scientific Director, IRP, NIDA, NIH, 5500 Nathan Shock Drive, Baltimore, Maryland 21224;
[3]University of Maryland School of Medicine, Baltimore, Maryland 21201; and
[4]Johns Hopkins School of Medicine, Baltimore, Maryland 21205

Cocaine is rapidly metabolized to major metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME), and minor metabolites, norcocaine, p-hydroxycocaine, m-hydroxycocaine, p-hydroxybenzoylecgonine (pOHBE), and m-hydroxybenzoylecgonine. This IRB-approved study examined cocaine and metabolite plasma concentrations in 18 healthy humans who provided written informed consent to receive low (75 mg/70 kg) and high (150 mg/70 kg) subcutaneous cocaine hydrochloride doses. Plasma specimens, collected prior to and up to 48 h after dosing, were analyzed by gas chromatography–mass spectrometry (2.5 ng/mL limits of quantification). Cocaine was detected within 5 min, with mean ± SE peak concentrations of 300.4 ± 24.6 ng/mL (low) and 639.1 ± 56.8 ng/mL (high) 30–40 min after dosing. BE and EME generally were first detected in plasma 5–15 min post-dose; 2–4 h after dosing, BE and EME reached mean maximum concentrations of 321.3 ± 18.4 (low) and 614.7 ± 46.0 ng/mL (high) and 47.4 ± 3.0 (low) and 124.4 ± 18.2 ng/mL (high), respectively. Times of last detection were BE > EME > cocaine. Minor metabolites were detected much less frequently for up to 32 h, with peak concentrations ≤ 18 ng/mL for all analytes except pOHBE (up to 57.7 ng/mL). These data improve our knowledge of the pharmacokinetics of cocaine and its major and minor metabolites in plasma following controlled subcutaneous cocaine administration.

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