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. Material and Methods Seven volunteers with a history of stimulant use received 4×10 mg (low) doses of sustained release S-(+)-MAMP HCl within one 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). Results MAMP Tmax occurred from 1 to 2 weeks after both doses, with Cmax ranging from 0.6–3.5 ng/mg after the low and 1.2–5.3 ng/mg after the high MAMP doses. AMP Cmax in hair was 0.1–0.3 ng/mg and 0.2–0.5 ng/mg, 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 cutoff for at least two 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 (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 Cmax 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.

Validation and application of hair analysis for the detection of methamphetamine in young Thai adults

“…The results indicated no linear correlation (r 2 = 0.01), consistent with findings previously reported [23,24]. Explanations include differences in individual metabolism, differences in hair melanin content, variations in the incorporation of the drug into hair, hair hygiene, and perhaps most importantly, the reliability of self-reported drug use [23,25]. In animal studies, in which the delivered drug dose is controlled, a correlation between dosages and drug concentrations in hair has been demonstrated [26].…”

“…In animal studies, in which the delivered drug dose is controlled, a correlation between dosages and drug concentrations in hair has been demonstrated [26]. Recently, a similar correlation has been established for human subjects [25].…”

Exposures associated with clandestine methamphetamine drug laboratories in Australia

“…It is suggested (191) that some of these variability issues may be due to the variety of assay protocols utilised in these studies or melanin concentrations in hair (where a significant correlation has also been observed) (199). Regardless of the variability observed it still holds that the higher the dose the higher the concentration in hair.…”

“…While the nature of the interaction has not been established a significant correlation has been observed in controlled human studies (199).…”

“…A positive linear relationship between dose and hair concentration has been identified for cocaine and medicinal drug use (200) with segmented analysis of hair used to evaluate changes in dose over time (201,202). In relation to use of methamphetamine, a positive dose-response relationship has been demonstrated with rat hair (203), in drug users (204) and in a controlled study (199).…”