Distribution of amphetamine, benzoylecgonine, cocaethylene, cocaine, fentanyl, and methamphetamine in seven regions of the brain

Brain tissue is a potentially valuable postmortem specimen because of its relative anatomical isolation, reduced susceptibility to postmortem degradation, and relevance as the primary site of action for many drugs. Despite the frequent detection of stimulants and synthetic opioids in medicolegal death investigations, limited data exist regarding their regional distribution within the human brain. This study evaluated the distribution of amphetamine (AMP), methamphetamine (MAMP), cocaine, benzoylecgonine, cocaethylene, and fentanyl across seven anatomically distinct brain regions (basal ganglia, cerebellum, medulla, midbrain, occipital lobe, thalamus, and pons) in postmortem human cases. Brain samples were collected from cases screening positive for cocaine/benzoylecgonine or fentanyl using urine drug screening at autopsy. Brain homogenates were extracted in triplicate using solid-phase extraction followed by instrumental analysis using liquid chromatography tandem mass spectrometry. To make comparisons between cases, concentrations were normalized to the occipital lobe. Statistical analysis using one-way ANOVA determined that there were significant differences in concentrations within cases and normalized concentrations between cases. The basal ganglia had the highest concentrations for AMP, cocaethylene, cocaine, fentanyl, and MAMP. Benzoylecgonine concentrations were highest in the cerebellum. Concentrations of metabolite to parent compound showed that there were weak correlations between benzoylecgonine-to-cocaine, cocaethylene-to-cocaine, and AMP-to-MAMP. While there was heterogeneous distribution in the brain, any of the brain regions included in this study could have utility for postmortem toxicology testing as analytes were generally detected in all examined brain regions. The basal ganglia typically had highest concentrations in this study and therefore are recommended for collection.