A Validated Method for the Simultaneous Determination of Quetiapine, Clozapine and Mirtazapine in Postmortem Blood and Tissue Samples

Psychotropic drugs are regularly present in cases of sudden, unexpected death. Such drugs also tend to express significant postmortem redistribution. To facilitate further investigation of this phenomenon, reliable quantitative methods applicable to multiple biological matrices are needed. We present a validated ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of quetiapine, clozapine and mirtazapine in postmortem whole blood, skeletal muscle, brain tissue and liver tissue using high-performance liquid chromatography-tandem mass spectrometry. Sample preparation was performed using liquid-liquid extraction. The validated ranges were 3.8-1534, 16-1960 and 13-1060 mu g/L for quetiapine, clozapine and mirtazapine, respectively. Within-run and between-run accuracy (87.4-122%) and precision (CV 1.5-8.9%), matrix effects (95-101%) and recovery (35.7-92%) were validated at two concentration levels; 5.8 and 1227 mu g/L for quetiapine, 25 and 1568 mu g/L for clozapine and 20 and 849 mu g/L for mirtazapine. Stability in a 10 degrees C environment was assessed for treated samples of brain, liver and muscle tissue, showing deviations in analyte concentrations ranging from -8% to 9% after 3 days. The analyte concentrations in treated samples of whole blood stored at 4 degrees C deviated by <5% after 5 days. The method was applied in three forensic autopsy cases implicating quetiapine, clozapine and mirtazapine, respectively, in supratherapeutic concentrations.