From Blood to Brain: Postmortem Brain Concentrations and Brain-Blood Ratios of Chlorprothixene, Clozapine, Olanzapine and Quetiapine

Abstract Treatment with antipsychotics such as chlorprothixene, clozapine, olanzapine and quetiapine can be associated with cardiovascular and metabolic risks and poisoning, making them highly relevant in toxicological investigations. Since antipsychotics primarily act within the central nervous system, brain tissue serves as an alternative or complementary matrix to femoral blood in toxicological analysis. This study aimed to retrospectively evaluate brain concentrations and brain-blood ratios across toxic and non-toxic levels in 466 postmortem cases involving chlorprothixene, clozapine, olanzapine and/or quetiapine. Median concentrations in brain tissue across all cases were 0.20 mg/kg for chlorprothixene, 4.2 mg/kg for clozapine, 0.42 mg/kg for olanzapine and 0.34 mg/kg for quetiapine. Corresponding brain-blood ratios remained stable across the examined concentration range with median ratios of 3.1 for chlorprothixene, 2.9 for clozapine, 2.6 for olanzapine and 3.0 for quetiapine. The provided brain concentrations and ratios can support further toxicological evaluations of postmortem cases.