To highlight issues still unsolved in hair analysis.

This lecture delves into the incorporation of xenobiotics into hair, focusing on their interpretation in forensic and clinical toxicology. It addresses three pivotal questions central to hair analysis: (1) was a drug administered?, (2) how much drug was administered?, (3) when was the drug administered? These questions, while seemingly straightforward, reveal complexities due to possible external contamination, individual biological variability, and limitations in analytical methodologies.

Determining whether a drug was truly administered or merely the result of external contamination is still a significant challenge in hair analysis. This lecture underscores the critical role of metabolites, which are formed exclusively through systemic metabolism, as markers to confirm drug intake. Such metabolites are absent in environmental sources of contamination, such as drug powders or plant material. However, some drugs, like cocaine, present unique challenges; the presence of primary metabolites like benzoylecgonine does not definitively rule out external contamination. To mitigate these issues, advanced metabolite profiling, including the detection of minor cocaine metabolites has been employed, although further research is required.

Estimating the amount of drug administered based on hair analysis remains elusive. While dose-to-concentration relationships are evident under controlled conditions, they are influenced by numerous factors, including hair pigmentation, individual metabolism, and drug properties. For example, melanin has a strong affinity for weakly basic drugs, such as amphetamines and cocaine, leading to higher drug concentrations in darker hair. Controlled studies with heroin and methamphetamine demonstrate dose-dependent increases in hair concentrations, yet the wide variability precludes dose estimations. Instead, hair concentrations may more effectively be used to categorize drug usage patterns into light, moderate, or heavy use. This approach, while less precise, provides valuable context in clinical and forensic settings. While these group-level patterns are informative, this lecture emphasizes that quantitative interpretations should always consider individual variability.

Segmental hair analysis offers temporal insights into drug administration by correlating drug incorporation with the hair growth cycle. However, an individual's hair growth rate is not known and a mean value of the hair growth rate is commonly used when performing and interpreting segmental hair analysis. Controlled studies involving single-dose administrations show that drugs can be detected in hair for months post-intake, with concentrations peaking in segments corresponding to the time of administration. However, the precision of timing decreases with longer intervals between drug intake and hair sampling due to diffusion and environmental influences and is also influenced by the segment length used. Although single-use scenarios pose great challenges, they can still provide approximate timelines when combined with knowledge of hair growth rates and segment lengths.

In conclusion, hair analysis is a robust method for investigating drug use, providing qualitative and, to some extent, quantitative insights into whether a drug was administered, the general magnitude of drug exposure, and the timing of use. However, limitations persist, including susceptibility to external contamination, inter-individual variability, and the inability to quantify precise doses or exact timing without supplementary evidence. By combining hair analysis with other investigative tools, toxicologists can achieve a comprehensive understanding of drug use patterns.