Assessing the stability of drugs of abuse and pharmaceuticals in postmortem blood samples

Reliable toxicological analysis is crucial for accurate forensic and clinical interpretation; however, pre-analytical factors such as handling and storage can significantly alter drug concentrations in postmortem (PM) samples, potentially leading to misinterpretation. Postmortem degradation, influenced by enzymatic and microbial activity, can change drug levels, making it essential to understand drug stability in biological matrices.

This preliminary study investigates the long-term stability of drugs of abuse and psychoactive substances in PM blood samples from drug-related deaths stored at -20°C for 29 months.

Postmortem blood samples were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) following the routine methodology currently in use in the forensic toxicology laboratory. Stability was assessed by measuring concentration changes between analyses performed shortly after sample collection and reanalyses conducted after 6-29 months. Regression analyses were used to relate percentage variation in concentration to elapsed time.

A strong correlation was found between the percentage reduction in drug concentration and storage time for all tested molecules, including morphine, cocaine, methadone, ketamine, benzodiazepines, antidepressants, antipsychotics, and lidocaine. Regression curve analysis revealed a reduction in concentration beginning within the initial months, with high variability.

The study highlights the significant impact of long-term storage on drug concentrations in PM blood, emphasizing the need for careful consideration of storage intervals when reanalysis of samples is requested for forensic purposes. The findings underscore the importance of understanding degradation patterns for the accurate interpretation of toxicological results in medicolegal investigations.