Identification of a postmortem redistribution factor (F) for forensic toxicology

Abstract

Background: Postmortem redistribution (PMR) refers to the changes that may occur in drug concentrations after death. Consequently, postmortem concentrations in blood may not always replicate the antemortem drug levels. Literature supports the model describing drugs with a liver (L) concentration to peripheral blood (P) concentration ratio less than 5 (L/kg) being prone to little or no PMR. Conversely, drugs with a L/P ratio greater than 20 to 30 (L/ kg) have propensity for substantial PMR. Findings: Expanding upon this prior work, the current paper presents the concept of a postmortem redistribution factor (F) for a drug, which characterizes the direct relationship between postmortem peripheral blood and the corresponding antemortem whole blood concentration. Conclusions: Development of the concept of a "postmortem redistribution factor" will provide a more definitive and authoritative drug ranking, and possibly, numerical interpretation of PMR for forensic toxicologists.

Comparative Study of Drug Interactions in Benzodiazepine Associated Deaths

“…Regarding the substances detected in the presented cases, for phenobarbital, alprazolam, codeine, carbamazepine, the postmortem blood/therapeutic plasma concentration ratio is 1, suggesting that in a comprehensive postmortem data set, median postmortem concentration is within the established therapeutic range [17]. For doxepin and fluvoxamine, this ratio was 3, for midazolam is 2, and for levomepromazine, 16. This suggests that postmortem concentrations might be somewhat higher than they are antemortem due to postmortem redistribution of drugs.…”

“…A liver/blood ratio of >4 indicates death occurred Table 2 TOXICOLOGICAL ANALYSIS RESULTS within 5 h of ingestion [15]. An F factor (antemortem concentration = postmortem concentration/F) as a means of identifying drug redistribution was proposed [16]. After a recent extensive study, a post-mortem blood/plasma relationship was calculated for each drug [17].…”

Analytical data supporting the “theoretical” postmortem redistribution factor (Ft): a new model to evaluate postmortem redistribution

“…Table 1 presents recently published median L/P ratio data for 867 cases where 44 drugs were examined [ 19 ]. Using these data, supplementary investigations were then undertaken to advance the concepts of the PMR factor ( F ) [ 21 ], and the “theoretical” PMR factor ( F t ) [ 22 ].…”

“…Furthermore, a direct correlation between the postmortem peripheral blood and corresponding antemortem concentration has been published [ 20 ]. Based upon this work, a PMR factor was defined – a factor ( F ) that expressed the direct relationship between postmortem peripheral blood and the corresponding antemortem whole-blood concentration [ 21 ]. More recently, this concept was expanded with the development of an equation to determine a “theoretical” postmortem redistribution factor ( F t ) based upon a drug's unique L/P ratio – the only independent variable [ 22 ].…”

Interpreting postmortem drug analysis and redistribution in determining cause of death: a review

“…The same author has further expanded this hypothesis to include an "F" factor (antemortem concentration = postmortem concentration/F) as a means of identifying drug redistribution. 52 Application of this factor will require the acquisition of a larger database than is available at present, particularly as measurement of liver concentrations is not without difficulties such as matrix effects. It is also not measured as a routine test in many laboratories.…”