Determination of postmortem redistribution and stability of opioids and its metabolites in opioid-related deaths

Changes in drug concentrations often occur after death by passive diffusion from the reservoir organs to the blood or from the blood to the organs. This phenomenon is called postmortem redistribution (PMR). It is thought that all drugs can be affected to some degree by PMR, and the major contributing factors are the time between death and sampling, sampling location and technique, potential postmortem metabolism/production of body enzymes or bacteria, and finally the physicochemical properties of the drug. One of the difficulties in interpreting toxicological findings together with PMR is to evaluate the effect of pharmacokinetic and pharmacodynamic interactions of drugs on PMR in polypharmacy cases. In this study, 96 rats divided into 6 groups were injected intravenously specific doses of heroin-codeine, heroin-fentanyl, heroin-dextromethorphan-paracetamol-caffeine combinations as well as heroin, codeine and morphine. Tissue and body fluid samples were collected from different regions in the time of death, postmortem 1st hour, 4th hour and 24th hours. All samples were extracted and analyzed by LC-MS/MS (liquid chromatography-tandem mass spectrometry). In this study, in-vivo postmortem pharmacokinetics and tissue distributions of opioid drugs were evaluated by determining the levels of opioid drugs and their metabolites in all biological samples collected. Morover, the effects of possible interactions of these drugs on the postmortem pharmacokinetics of the parent drug and its metabolites were evaluated in combinations of morphine-codeine, heroin-fentanyl, heroin-dextromethorphan-paracetamol-caffeine.