Postmortem redistribution of drugs: a literature review

Abstract

Postmortem drug analysis is crucial in identifying the potential cause and manner of death. However, it is threatened by a significant phenomenon called postmortem redistribution (PMR), which refers to the alterations in drug levels occurring after death. This review aims to describe the PMR phenomenon, the mechanisms involved in the PMR of drugs, the various methods used to predict it, and various artifacts of postmortem drug concentrations. Several mechanisms, including passive diffusion from solid organs that act as drug reservoirs to the surrounding tissues, cadaveric changes after death (e.g., cell death, blood coagulation, hypostasis, and movements), and the putrefactive process, can result in artifacts of postmortem drug concentrations. The drug's chemical and pharmacokinetic properties (such as acidic/basic properties, lipophilicity, protein binding, high volume of distribution, and residual metabolic activity) are additional factors. Several markers, including cardiac blood-to-peripheral blood ratio (C/P), liver-to-peripheral blood ratio (L/P), amino acid markers such as methionine, quantitative structure-activity relationship (QSAR) approach, and F factor, have been proposed for interpreting the liability of drugs to PMR. Several artifacts may affect the reliability of postmortem drug analysis. Peripheral blood is preferred for postmortem drug sample collection. Numerous laboratories evaluate the redistribution potential of drugs after death using the C/P concentration ratio. Nevertheless, the L/P concentration ratio is proposed to be a more reliable marker for PMR determination.

Keywords: Cardiac blood; Drugs; Liver; Peripheral blood; Postmortem redistribution; Postmortem toxicology; Ratio.