Elsevier

Analytica Chimica Acta

Volume 726, 13 May 2012, Pages 35-43
Analytica Chimica Acta

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

https://doi.org/10.1016/j.aca.2012.01.042Get rights and content

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 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 Tmax occurred from 1 to 2 weeks after both doses, with Cmax 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 Cmax 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 (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.

Highlights

► We studied in vivo incorporation of methamphetamine in human head hair. ► Methamphetamine (40 and 80 mg) was administered under controlled conditions. ► Methamphetamine and amphetamine incorporation was followed for 3 weeks. ► Influence of various factors (e.g. pre-analytical washing, melanin) was studied. ► Criteria to ascertain MAMP use based on MAMP/AMP ratio and AMP cut-off are proposed.

Introduction

Hair analysis has gained a well established role in forensic and clinical testing for past exposure to drugs. Advantages of hair testing as compared to analyses of other matrices for drugs is the much wider window of drug detection, enabling assessment of drug exposure well beyond the period of drug elimination from blood and urine. Additional advantages are the possibility of segmental analysis to document drug use history over time, and the detection of parent compounds, often permitting discrimination between different sources of exposure (e.g. heroin use from morphine or codeine intake). Practically, hair testing offers significant advantages, as its collection and storage are simple and inexpensive, as compared to other body fluids.

Nevertheless, many issues remain under discussion, including those of environmental contamination and removal of drugs due to different types of cosmetic treatments, and the ability of pre-analytical washing(s) of hair to remove external contamination and spare “actively” incorporated drug. Cut-off concentrations and analytes to discriminate between drug use and passive exposure (e.g. to smoked drugs), the lag time before a positive hair sample can be obtained after intake, and the role of melanin in drug incorporation, and correlations between dose and concentrations in hair are not yet fully understood.

The present work investigated some of these knowledge gaps through a controlled human study of the disposition of drugs in hair following oral methamphetamine administration. The incorporation of methamphetamine and its metabolite amphetamine in head hair was followed for a 3-week period after administration of two different methamphetamine dosages (4 × 10 mg and 4 × 20 mg), and methamphetamine and amphetamine concentrations were determined in discreet weekly hair samples collected by shaving the head, as well as in the respective hair wash solutions.

Section snippets

Protocol of drug administration

Seven volunteers with a history of stimulant use provided written informed consent to participate in a 10-week inpatient study approved by the National Institute on Drug Abuse (NIDA) Institutional Review Board and conducted at the Clinical Research Unit of the NIDA Intramural Research Program. Subjects’ characteristics are listed in Table 1. Before admission, subjects were submitted to clinical and psychological evaluations. During the study, individuals were kept under 24-h medical

Determination of methamphetamine and amphetamine in hair

Typical equation curves (1/x weighted regression analysis) were y = 1.842x + 0.004 (MAMP), y = 0.909x + 0.007 (AMP), where y is the peak-area ratio (analyte/internal standard) and x is the theoretical concentration. Correlation coefficients were higher than 0.999.

Intra- and inter-day imprecision and bias for MAMP and AMP are shown in Table S1.

The limit of quantification was established at 0.005 ng mg−1 for MAMP and AMP on the basis of the bias and imprecision of the determinations at this concentration

Discussion

Hair analysis is typically employed for the assessment of repeated or chronic exposure to drugs in different settings [10], [11]. In postmortem toxicology, hair analysis may be useful for the assessment of naïve [12] or chronic [13] MAMP intake, in order to evaluate a subject's tolerance. Analysis of maternal and neonatal hair is also a valid tool to assess intrauterine exposure to MAMP [14].

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