Incorporation of methamphetamine and amphetamine in human hair following controlled oral methamphetamine administration

Background: Although hair testing is well established for the assessment of past drug exposure, uncer-tainties persist about mechanisms of drug incorporation into hair and interpretation of results. The aim of this study was to administer methamphetamine (MAMP) under controlled conditions as a model drug to investigate drug incorporation into human hair. Material and methods: Seven volunteers with a history of stimulant use received 4 7 10 mg (low) doses of sustained release S-(+)-MAMP HCl within 1 week, with weekly head hair samples collected by shaving. 3 weeks later, 4 of them received 4 7 20 mg (high) doses. After extensive isopropanol/phosphate buffer washing of the hair, MAMP and its metabolite amphetamine (AMP) concentrations were determined in all weekly hair samples by LC\u2013MS\u2013MS in selected reaction monitoring mode with the undeca- and deca-deuterated drugs, respectively, as internal standards (LLOQ, 0.005 ng mg 121). Results: MAMP Tmaxoccurred from 1 to 2 weeks after both doses, with Cmaxranging from 0.6 to 3.5 ng mg 121 after the low and 1.2 to 5.3 ng mg 121 after the high MAMP doses. AMP Cmaxin hair was 0.1\u20130.3 ng mg 121 and 0.2\u20130.5 ng mg 121 , respectively, for low and high doses. Highly dose-related concentrations within subjects, but large variability between subjects were observed. MAMP concentrations were above the 0.2 ng mg 121 cut-off for at least 2 weeks following administration of both low and high doses. The overall AMP/MAMP ratio ranged from 0.07 to 0.37 with a mean value of 0.15 \ub1 0.07, and a median of 0.13. The percentage of MAMP and AMP removed with the washing procedure decreased with time after administration. A strong correlation was found between area under the curve of MAMP (r2 = 0.90, p = 0.00) and AMP (r2 = 0.94, p = 0.00) concentrations calculated for the 3-week period following administration and the total melanin concentration in hair. Significant correlations were observed also between Cmaxand melanin. Conclusions: This study demonstrated that despite large inter-individual differences, the incorporation of MAMP and AMP into hair is dose-related with much of the observed scatter of MAMP and AMP concentrations explained by melanin concentration in hai