A Systematic Review of Metabolite-to-Drug Ratios of Pharmaceuticals in Hair for Forensic Investigations

Abstract

After ingestion, consumed drugs and their metabolites are incorporated into hair, which has a long detection window, ranging up to months. Therefore, in addition to conventional blood and urine analyses, hair analysis can provide useful information on long-term drug exposure. Meta-bolite-to-drug (MD) ratios are helpful in interpreting hair results, as they provide useful information on drug metabolism and can be used to distinguish drug use from external contamination, which is otherwise a limitation in hair analysis. Despite this, the MD ratios of a wide range of pharmaceuticals have scarcely been explored. This review aims to provide an overview of MD ratios in hair in a range of pharmaceuticals of interest to forensic toxicology, such as antipsychotic drugs, antidepressant drugs, benzodiazepines, common opiates/opioids, etc. The factors influencing the ratio were evaluated. MD ratios of 41 pharmaceuticals were reported from almost 100 studies. MD ratios below 1 were frequently reported, indicating higher concentrations of the parent pharmaceutical than of its metabolite in hair, but wide-ranging MD ratios of the majority of pharmaceuticals were found. Intra- and interindividual differences and compound properties were variables possibly contributing to this. This overview presents guidance for future comparison and evaluation of MD ratios of pharmaceuticals.

Interpretation of hair and nails findings in an infant death case related to maternal addiction to tramadol

“…In contrast, the mother's hair had high and mostly stable TR concentrations throughout her hair strand. In addition, MRs in the mother's hair are much higher than those in hair of her children, in the range of MRs typically observed in patients undergoing TR treatment 28,29 . Ultimately, the results in the mother's hair are consistent with a regular TR use as she admitted.…”

“…Nevertheless, contribution of sweat/sebum during the agony phase to the hair concentration pattern cannot be ruled out as a morphine concentration increase from proximal to distal has been also described (in two out of the three reported cases) in segmented hair analysis due to recent sweat contamination during the phase of agony in opioid‐related intoxication with well‐documented opioid abstinence before death 18 . Anyway, the hypothesis of external contamination (rather than repeated administrations of TR in the weeks before death) of the infant's hair is supported by the low MRs (<0.1), similar to MR ranges previously observed in hair of employees of a pharmaceutical company producing TR (working within the production site or in production control laboratories) 28,29 …”

“…18 Anyway, the hypothesis of external contamination (rather than repeated administrations of TR in the weeks before death) of the infant's hair is supported by the low MRs (<0.1), similar to MR ranges previously observed in hair of employees of a pharmaceutical company producing TR (working within the production site or in production control laboratories). 28,29 Regarding the sister's hair results, TR concentrations are lower than those observed in the infant's hair. However, there is also an increase of the TR concentration from proximal to distal hair segment and MRs are also very low in the sister's hair.…”