Role of metabolites in aviation forensic toxicology

In aviation accident investigations, specimens from fatal aircraft victims are analyzed for drugs. The presence of drugs suggests possible associated medical conditions for which they might have been taken. As drugs are mostly present in therapeutic to subtherapeutic levels in aviation forensic toxicology cases, determination of parent drugs and their metabolites in multispecimens is of significance. Although chemically reactive metabolites are difficult to detect, physiologically active and inactive metabolites can be analyzed. Selective and sensitive techniques are available, but unavailability of metabolite reference standards, endogenous substance interference, and low tissue metabolite levels limit the analyses. However, the majority of primary metabolites can be effectively characterized/quantitated. Demonstrating the presence of drug (e.g., terfenadine, cocaine, THC) metabolites provides a compelling evidence for exposure to the parent drug and facilitates interpretation of results, particularly when the metabolites are active. Such analyses are not as helpful if the metabolites are also available as drugs (e.g., diazepam, temazepam, oxazepam).