Occipital Lobe to Femoral Blood Ratios of Amphetamine, Methamphetamine, Cocaine, Benzoylecgonine, Cocaethylene, and Fentanyl in Postmortem Cases

Abstract Interpretation of postmortem toxicology results is complicated by postmortem redistribution (PMR), which can alter drug concentrations between tissues and blood (BL). This study evaluates brain (BR) to BL concentration ratios for amphetamine (AMP), methamphetamine (MAMP), cocaine (COC), benzoylecgonine (BE), cocaethylene (CE), and fentanyl (FENT) using postmortem casework data to evaluate the utility of BR tissue as an alternative matrix. BR:BL ratios varied widely across analytes: AMP (2.2–5.8), BE (0.2–2.1), CE (1.2–5.1), COC (0.1–5.8), MAMP (2.2–7.3), and FENT (1.1–24.8). Lipophilic compounds (AMP, CE, COC, MAMP, FENT) generally exhibited ratios greater than one, consistent with preferential BR partitioning and susceptibility to PMR, whereas the polar metabolite BE showed ratios less than one, reflecting limited BR accumulation. FENT demonstrated the greatest variability, highlighting challenges in interpreting its postmortem concentrations. Correlations between BR and femoral BL concentrations were slightly positive for all analytes, indicating that BR concentrations may not be reliable proxies for BL levels. Evaluation of select antemortem cases and outliers revealed additional influences on BR:BL ratios, including survival time, drug stability, route of administration, and polysubstance use. COC instability and hydrolysis to BE, as well as incomplete drug distribution in rapid deaths, contributed to atypical ratios. Overall, BR:BL ratios are highly analyte dependent and influenced by both pharmacokinetic properties and postmortem factors. While BR tissue may provide useful complementary information when BL is unavailable, it should not be used as a direct substitute for BL in toxicological interpretation. These findings underscore the need for further research to expand BR:BL datasets across drug classes.