Analytical and Toxicological Aspects of Drug Incorporation into Human Hair
Abstract: The overall purpose of this thesis was to develop analytical methods for the determination of drugs and melanin content of human hair for practical use in forensic and clinical toxicology. The thesis consists of five papers, two of which are controlled single dose studies where codeine or selegiline were administered to healthy volunteers. One patient study, looked at the concentrations of selegiline metabolites in both pigmented and senile white hairs as well as plasma. Another study involved forensic autopsy cases where the occurrence of drugs of abuse in post-mortem blood, urine and hair were compared. Finally, one in vitro study investigated the binding of [3H]-flunitrazepam to melanin. To our knowledge, the controlled dosage studies are the first to quantitatively determine the relationship between drug concentration in human hair and melanin content.The results demonstrated that pigmentation was an important factor for the incorporation of codeine, methamphetamine, and amphetamine into human hair. The relationships could be described by exponential functions with correlations coefficients r2>0.8. We have shown that the pigmented portion of hair from grey-haired patients incorporated more methamphetamine and amphetamine than the non-pigmented portion. The mean pigmented/white-hair ratios were 3.7±1.9 and 3.0±1.2 for methamphetamine and amphetamine respectively. Segmental hair analysis showed decreasing drug-concentrations over three months as a sign of noncompliance or of instability of the drugs in hair owing to cosmetic treatment of hair or wear. In the controlled studies, we demonstrated that the drug concentration in hair was fairly constant up to one month. In the study on autopsy cases, we found that hair analysis revealed patterns of multi-drug use not found by analysis of a single blood sample. Also, in 6 of 19 cases of heroin overdose, no opiates could be detected in hair. This suggested "first" or only occasional use of heroin, which might have been a contributing factor to the overdose death, because of lack of tolerance. The results from the in vitro study showed that binding of flunitrazepam to eumelanin occurs by two mechanisms, a Langmuir-like binding and a diffusion limited binding. We propose that these are expressions of an initial binding to the melanin surface (surface binding) followed by the diffusion of drug molecules into the melanin granule (bulk binding).Hair as a specimen for toxicological analysis has hitherto not been investigated in Sweden. This thesis address questions raised by international research on the incorporation of drugs into hair and its implications for clinical and forensic toxicology.Melanin has been established as an important factor for incorporation and binding of certain drugs into human hair and methods that allow correction for this are presented. Together, the results from the various studies provide a framework for both future research and the start of drug analysis in hair for forensic and clinical applications in Sweden.
This dissertation MIGHT be available in PDF-format. Check this page to see if it is available for download.