Identification of postmortem paliperidone metabolite in human blood by LC–Q-Orbitrap-MS.

This article focuses on the postmortem decomposition of paliperidone, a second-generation atypical antipsychotic drug, by hemoglobin (Hb) through the Fenton reaction, which affects the accurate determination of its blood concentration in forensic toxicology. The study identifies a temperature-dependent cleavage of paliperidone’s C–N bond linker by Hb, producing a unique metabolite named 6-fluoro-3-(4-piperidinyl)benzisoxazole (PM1), detected in both experimental Hb/H2O2 solutions and postmortem blood samples from individuals who died after ingesting paliperidone. These findings suggest that PM1 may serve as a biomarker to correct paliperidone blood levels at the time of death, addressing discrepancies between concentrations measured at autopsy and at death. Temperature was found to significantly influence paliperidone degradation, while pH had a lesser effect within physiological ranges. The study proposes further research to validate PM1’s utility in forensic investigations.