A Mechanism-Based Forensic Investigation into the Postmortem Redistribution of Morphine

Abstract

Abstract The interpretation of postmortem drug levels is complicated by the change in drug blood levels during the postmortem period, a phenomenon known as postmortem drug redistribution. We investigated the postmortem redistribution (PMR) of morphine, morphine-3-glucuronide and normorphine in the rat. Morphine (10 mg/kg) was intravenously injected into rats, followed by euthanasia 1 h post-injection. The carcasses were placed in a supine position at room temperature, and tissues including heart blood, femoral blood, liver, lung and brain were collected at different time points: 0, 8, 16 or 24 h postmortem. The samples were analyzed with a validated (following modified Scientific Working Group for Forensic Toxicology (SWGTOX) (20) guidelines) liquid chromatography–tandem mass spectrometry method. The use of a mechanism-based approach (involving the used set doses of drug with the study performed in controlled environment) to assess PMR using systematic and statistical analyses provides important information that has not previously been presented in PMR literature. While previous human studies focus on central to peripheral ratios as well as peripheral to tissue ratio, this work focused on the change in morphine and metabolite concentrations over the course of the postmortem interval in relation to each other in addition to the comparison to additional matrices at each postmortem interval. Postmortem redistribution was identified in several tissues across the postmortem interval; however, there was minimal statistical difference observed among each matrix at a given postmortem interval with the exception of normorphine and morphine-3-glucuronide. Combined, our study provides a valuable resource and reference information that can aide toxicologists, medical examiners or coroners when assessing postmortem drug concentrations of morphine and metabolites when they are making determinations of cause of death.