Post mortem tissue distribution of quetiapine in forensic autopsies

Abstract

The antipsychotic drug quetiapine is widely used, and increasingly prescribed off-label. Furthermore, quetiapine use has been linked to increased mortality rates, most likely due to a range of cardiovascular and metabolic adverse effects. This makes quetiapine a relevant substance in forensic toxicology casework. Quetiapine is believed to undergo significant post mortem redistribution. Herein, we present tissue distribution and concentration levels of quetiapine in post mortem whole blood, brain tissue, skeletal muscle, and liver tissue in a series of 14 quetiapine-implicated forensic autopsy cases along with the quetiapine concentrations determined in femoral whole blood in conjunction with the autopsies. Quantification was performed using liquid-liquid extraction and a validated UPLC-MSMS method. Six deaths were attributed to intoxication with quetiapine in combination with other substances; there were no quetiapine monointoxications. In eight cases, death was attributed to other causes than drug toxicity. In a majority of the cases, liver tissue contained the highest quetiapine concentrations, while whole blood levels were the lowest. Central (heart) blood concentrations were generally higher than peripheral (femoral) blood levels. Quetiapine concentrations in femoral blood correlated most strongly with concentrations in skeletal muscle. Otherwise, there was no consistent hierarchy of quetiapine tissue concentrations, and the tissue distribution showed no clear relationship with the length of the post mortem interval.