Investigations into the stability of 17 psychoactive drugs in a “simulated postmortem blood” model

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.