Literature review on forensic implications of illicit drug metabolism: A medicinal chemistry perspective.

The metabolic processes of illicit substances are crucial within the realm of forensic toxicology, affecting the detection, analysis, and interpretation of drugs in legal and investigative contexts. Substances like opioids, cannabinoids, hallucinogens, benzodiazepines, and novel psychoactive substances (NPS) experience metabolic alterations primarily through Phase I (oxidation, reduction, hydrolysis) and Phase II (glucuronidation, sulfation) transformations. Fundamentally governed by cytochrome P450 (CYP) enzymes, they significantly influence the detectability and potential toxicity of the compounds. Specific metabolites, including 6-monoacetylmorphine (6-MAM) derived from heroin, benzoylecgonine originating from cocaine, and THC-COOH from cannabis, act as essential forensic indicators that assist in identifying patterns of substance use, recent exposure, or post-mortem drug redistribution. Nonetheless, drug metabolism exhibits substantial variability influenced by factors such as genetic polymorphisms, fluctuations in enzyme activity, and drug interactions, which can complicate forensic evaluations. Particularly those associated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high-resolution mass spectrometry (HRMS), have significantly bolstered the accuracy and consistency of drug identification across biological specimens like blood, urine, hair, and vitreous humor. This manuscript explores the forensic significance of drug metabolism and underscores its relevance in workplace drug testing, cases of impaired driving, and post-mortem toxicological investigations.