Thinking beyond blood: Brain concentrations and brain-blood ratios in postmortem toxicology

Toxicological analysis is an integral part of forensic death investigations. However, analysis is sometimes complicated by postmortem changes, and blood might not always be useable or available due to postmortem redistribution or degradation. In these cases, brain tissue can be useful as the brain is more protected against trauma, putrefaction, postmortem redistribution, skeletonization and severe blood loss. However, reference concentrations of drugs in brain tissue are still scarce. This study aimed to report brain concentrations and brain-blood ratios for 122 compounds including drugs of abuse, pharmaceuticals, and metabolites frequently detected in forensic autopsy cases. In total, 2264 cases were collected over an 11-year period and retrospectively categorized as having either toxic or therapeutic levels of detected compounds based on blood concentrations. Toxic and therapeutic concentrations showed considerable overlap in both blood and brain due to drug tolerance and multi-drug combinations. Brain-blood ratios were highest for compounds with direct function on the central nervous system, especially antidepressants and sedative-hypnotics. The reported brain concentrations and brain-blood ratios can serve as reference values for interpretation of drug concentrations in brain tissue and the evaluation of cause of death in future forensic investigations.