In the postmortem environment, some drugs and metabolites may degrade due to microbial activity, even forming degradation products that are not produced in humans. Consequently, underestimation or overestimation of perimortem drug concentrations or even false negatives are possible when analyzing postmortem specimens. Therefore, understanding whether medications may be susceptible to microbial degradation is critical in order to ensure that reliable detection and quantitation of drugs and their degradation products is achieved in toxicology screening methods. In this study, a “simulated postmortem blood” model constructed of antemortem human whole blood inoculated with a broad population of human fecal microorganisms was used to investigate the stability of 17 antidepressant and antipsychotic drugs. Microbial communities present in the experiments were determined to be relevant to postmortem blood microorganisms by 16S rRNA sequencing analyses. After 7 days of exposure to the community at 37°C, drug stability was evaluated using liquid chromatography coupled with diode array detection (LC‐DAD) and with quadrupole time‐of‐flight mass spectrometry (LC‐QTOF‐MS). Most of the investigated drugs were found to be stable in inoculated samples and noninoculated controls. However, the 1,2‐benzisothiazole antipsychotics, ziprasidone and lurasidone, were found to degrade at a rate comparable with the known labile control, risperidone. In longer experiments (7 to 12 months), where specimens were stored at −20°C, 4°C, and ambient temperature, N‐dealkylation degradation products were detected for many of the drugs, with greater formation in specimens stored at −20°C than at 4°C.

There are numerous biochemical and biological processes that occur after death that may have a significant influence on post-mortem drug concentrations. These processes may render the quantification of particular drugs unreliable, or even result in drugs being undetectable in some instances, despite the use of several methods. Problems may occur with changes in the drug concentration via bacterial degradation, residual tissue enzymatic activity, or via post-mortem redistribution from tissues of a higher to a lower concentration. Many analytical techniques can suffer from interferences due to co-extracted putrefactive compounds that mask or alter the way a drug is detected, depending on the analytical technique utilised. The following paper reviews problems associated with post-mortem drug concentration changes, and the significance of microbial influences during the post-mortem interval and sample storage.

The stability of two benzisoxazole antipsychotics was determined in vitro in decomposing porcine blood inoculated with bacteria, utilizing a high-performance liquid chromatography with ultraviolet and fluorescence detection method for drug quantitation. Stability experiments for risperidone and paliperidone were conducted at 7, 20 and 37°C for 4 days using sterile and bacterially inoculated porcine blood. The drugs were stable in sterile blood at each temperature and in inoculated blood at 7°C, but degraded significantly in inoculated blood at 20 and 37°C. Complete loss occurred within 2 days when incubated at 37°C. The benzisoxazole-cleaved degradation products for both drugs were identified as 2-hydroxybenzoyl-risperidone and 2-hydroxybenzoyl-paliperidone utilizing liquid chromatography quadrupole-time-of-flight mass spectrometry and accurate mass measurements. The degradation products have been found in postmortem case studies, including one case where risperidone and paliperidone were not detected, indicating complete conversion can occur in situ.