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Deuterium-labeled cocaine (cocaine-d5) was administered intravenously and/or intranasally in doses of 0.6-4.2 mg/kg to 25 human volunteers under laboratory clinical conditions. Sequential blood samples were collected for up to 3 days, and hair samples were collected for up to 10 months. Samples were analyzed by gas chromatography-mass spectrometry (GC-MS) for cocaine-d5 and its major metabolite, benzoylecgonine-d5 (BZE-d5). The parent drug, cocaine-d5, was the predominant analyte in hair, whereas BZE-d5 was the major analyte in blood, especially at later time periods. The amount of cocaine-d5 incorporated into hair ranged from 0.1 to 5 ng/mg hair, whereas the amount of BZE-d5 was approximately one-sixth of that concentration. The threshold dose for detection was estimated to be 25-35 mg of drug administered intravenously. A single dose could be detected for 2-6 months. Subjects receiving the same dose differed (from two to 12 times as much depending upon how it was measured) in the amount of cocaine-d5 incorporated into their hair. Non-Caucasians, in particular, incorporated more cocaine-d5 in hair than did Caucasians. Also, segmental analysis of the samples revealed considerable intersubject variability in the time drug first appeared in hair and the rate at which the drug moved along the hair shaft with time. These interindividual differences could not be explained by differences in plasma pharmacokinetics. Considered together, these results suggest that cocaine incorporation into hair may occur by way of multiple mechanisms--by way of sweat and sebum, for example--and at various times during the hair growth cycle. Thus, hair analysis using GC-MS appears to be a very sensitive method for detecting cocaine ingestion. However, within the range of doses used in the present study, hair does not provide a particularly accurate record of either the amount, time, or duration of drug use.

Incorporation of Isotopically Labeled Cocaine and Metabolites into Human Hair: 1. Dose-Response Relationships