The incorporation of cocaine and metabolites into hair: Effects of dose and hair pigmentation

The relationship between xenobiotic concentrations in hair and the degree o f systemic xenobiotic exposure is poorly defined. The purpose of this study was to evaluate the effect of dose, time, and pigment on the hair incorpor ation 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) on ce daily for 5 days. Fourteen days after the initial injection, the hair wa s collected and analyzed by gas chromatography/mass spectrometry for the co mpounds of interest. COC, EME, and NCOC were preferentially incorporated in to pigmented hair in a dose-dependent manner. None of the analytes were det ected in nonpigmented hair. The plasma pharmacokinetic profile of each anal yte was determined at each dose. After normalizing for the plasma concentra tions, the incorporation of COC into pigmented hair was 2 orders of magnitu de 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 conc entrations are reached in pigmented hair. In nonpigmented hair, concentrati ons 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-mediate d differences in the incorporation of COC and its metabolites noted at 14 d ays after dosing are also evident a few hours after drug administration.