title: Dose-concentration relationships in hair from subjects in a controlled heroin-maintenance program.
abstract: Hair specimens were collected from the vertex area of 20 subjects taking part in a heroin-maintenance program. Subjects were administered, under controlled conditions, heroin hydrochloride in 2 or 3 doses/day intravenously. Heroin doses ranged from 30 to 800 mg/day, and were self-administered. In all cases, a 4-cm segment from the proximal zone (root) was analyzed, which corresponded to about 100 days of hair growth. During that period, total heroin administered ranged from 14,100 to 71,540 mg. All special features of hair such as coloring, bleaching, etc. were noted. Each sample was washed twice with dichloromethane (5 mL, 2 min) and, after drying, cut into small pieces of approximately 1 mm. A 30-35-mg aliquot was incubated overnight at 45 degrees C in 1 mL methanol in the presence of 200 ng of heroin-d9, 6-acetylmorphine-d3, and morphine-d3. The methanolic extract was then evaporated to dryness, and the residue was derivatized by silylation (BSTFA + 1% TMCS). Drugs were analyzed by gas chromatography-mass spectrometry in electron impact mode. Limits of quantitation were set to 0.1 ng/mg. Concentrations ranged from 0 to 4.53, 0.38 to 10.11, and 0.71 to 5.20 ng/mg for heroin, 6-acetylmorphine, and morphine, respectively. 6-Acetylmorphine was the major analyte present in hair in all but five cases. Heroin was present in the highest concentration in three cases, and morphine was the major metabolite in two cases, probably because of hydrolysis. Subjects tested positive for heroin in all but two cases. No correlation between the doses of administered heroin and the concentrations of total opiates in hair was observed (r = 0.346). However, when considering a single analyte, it was observed that the correlation coefficient seemed to be linked to its plasma half-life. A weak correlation coefficient corresponds to a drug with a short plasma half-life, and the correlation coefficient increases when plasma half-life increases, as r = 0.12, 0.25, and 0.64 for heroin, 6-acetylmorphine, and morphine, respectively. These results suggest that using quantitative drug measurements in hair to determine the amount of drug ingested will remain inapplicable until more is known about the factors that may influence the incorporation of drugs into hair and a way to reduce the observed variability.
authors.affiliation: Institut de Médecine Légale, Strasbourg, France.
authors.forename: P
authors.initials: P
authors.lastname: Kintz
authors.forename: P
authors.initials: P
authors.lastname: Bundeli
authors.forename: R
authors.initials: R
authors.lastname: Brenneisen
authors.forename: B
authors.initials: B
authors.lastname: Ludes
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006197:Hair / Q000737:chemistry*; D006200:Hair Color; D003932:Heroin / Q000032:analysis* / Q000627:therapeutic use; D006556:Heroin Dependence / Q000378:metabolism / Q000534:rehabilitation*; D006801:Humans; D008297:Male; D009020:Morphine / Q000032:analysis; D009022:Morphine Derivatives / Q000032:analysis; D009294:Narcotics / Q000032:analysis* / Q000627:therapeutic use; D015813:Substance Abuse Detection / Q000379:methods*
chemical_list: D009022:Morphine Derivatives; D009294:Narcotics; D003932:Heroin; D009020:Morphine; C026979:6-O-monoacetylmorphine