title: Incorporation of methamphetamine and amphetamine in human hair following controlled oral methamphetamine administration.
abstract: BACKGROUND
  Although hair testing is well established for the assessment of past drug exposure, uncertainties 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.
  
  
  METHODS
  Seven volunteers with a history of stimulant use received 4×10 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 4×20 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-MS-MS in selected reaction monitoring mode with the undeca- and deca-deuterated drugs, respectively, as internal standards (LLOQ, 0.005 ng mg(-1)).
  
  
  RESULTS
  MAMP T(max) occurred from 1 to 2 weeks after both doses, with C(max) ranging from 0.6 to 3.5 ng mg(-1) after the low and 1.2 to 5.3 ng mg(-1) after the high MAMP doses. AMP C(max) in hair was 0.1-0.3 ng mg(-1) and 0.2-0.5 ng mg(-1), 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(-1) 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 ± 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 (r(2)=0.90, p=0.00) and AMP (r(2)=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 C(max) and 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 hair.
authors.affiliation: Department of Public Health & Community Medicine, University of Verona, Italy. aldo.polettini@univr.it
authors.forename: Aldo
authors.initials: A
authors.lastname: Polettini
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Cone
authors.forename: David A
authors.initials: DA
authors.lastname: Gorelick
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000661:Amphetamine / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006197:Hair / Q000737:chemistry*; D006801:Humans; D008297:Male; D008543:Melanins / Q000032:analysis; D008694:Methamphetamine / Q000032:analysis*; D053719:Tandem Mass Spectrometry
chemical_list: D008543:Melanins; D008694:Methamphetamine; D000661:Amphetamine