Population-Stratified Distributions of Post-Mortem Blood Drug Concentrations: An Epidemiological Framework for...

Interpretation of post-mortem drug concentrations remains a major challenge in forensic toxicology because factors, including post-mortem redistribution, drug tolerance, polypharmacy and inter-individual variability, limit the utility of fixed therapeutic, toxic or purportedly fatal concentration thresholds. Using data from the National Programme on Substance Use Mortality (NPSUM), we examined post-mortem blood drug concentrations within a population-based epidemiological framework. Quantitative concentration data were available for 93 psychoactive substances reported to NPSUM up to 1 November 2022. Concentrations were stratified by age, sex, ethnicity, prescription status, drug involvement in death and co-detection with other substances. Four exemplar drugs representing distinct pharmacological classes and toxicological profiles were selected for detailed evaluation: methadone, diazepam, 3,4-methylenedioxymethamphetamine (MDMA) and quetiapine. Quantifiable concentrations were available in 4514 methadone, 3482 diazepam, 540 MDMA and 677 quetiapine cases. Across all four drugs, concentration distributions demonstrated substantial variability and extensive overlap between deaths in which the drug was implicated and those in which it was not. Although some substances showed higher median concentrations in implicated cases, no concentration threshold reliably differentiated drug-related from non-drug-related deaths. Demographic stratification altered concentration distributions but did not materially improve discrimination. These findings suggest that extensive overlap in post-mortem drug concentrations is a fundamental characteristic of forensic toxicology data. Population-based concentration distributions provide important contextual information but should be interpreted within a holistic framework that incorporates pathological findings, clinical history, co-administered substances and the circumstances of death.