A validated GC/MS method for the investigation of quetiapine-related deaths in Greece

Abstract

Objective: Quetiapine is an atypical antipsychotic drug that is used to treat the symptoms of schizophrenia and other psychiatric disorders. During the last years, quetiapine has also been associated with cases of misuse and abuse, and there are strong indications that it possesses an addictive potential. A suitable method is necessary for the toxicological investigation of such cases. Materials and Methods: A simple gas chromatographymass spectrometric method was developed, validated, and applied for the determination of quetiapine in biological fluids during the investigation of quetiapine-related cases. The sample preparation procedure includes solid-phase extraction and silylation using N-methyl-N-tert-butyldimethylsilyl-trifluoroacetamide with 1% tert-butyldimethylsilylchloride. Results: The limits of detection and quantification were 1.50 and 5.00 ng/mL, respectively. The calibration curves were linear up to 2000 ng/mL (R 2 ≥ 0.991) and absolute recovery higher than 81%. Accuracy (intra-and inter-day) was found to be between −11.1 and 12.4%, whereas the precision was found to be <13.3%. The validated method was successfully applied to post-mortem blood samples during the toxicological investigation of 50 quetiapine-related sudden and violent deaths. Quetiapine was determined at toxic levels (>1800 ng/mL) in eight cases and at lower concentrations (5.21-1430 ng/mL) in the other 42 cases. It is remarkable to be mentioned that in all 50 cases one or more drugs were detected along with quetiapine. Conclusions: Quetiapine has been detected with increasing frequency in post-mortem cases in Greece during the last 3 years. This is in accordance with the growing concerns worldwide about the misuse or abuse of the drug and its contribution to the cause of death of quetiapine-related lethal cases. Physicians should be alert about the toxicity of quetiapine, its possible misuse or abuse, and its synergy with other drugs, medicinal or not, especially in patients under multiple drug therapy or drug addicts.