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Abstract
The antipsychotic drug clotiapine (Entumine® ) has been marketed for more than 35 years, however there is little published data on the therapeutic and toxic concentrations of this drug. To fill this gap, two rapid and sensitive methods were developed for the determination of clotiapine (2-chloro-11-(4-methyl-1-piperazinyl)dibenzo-[b ,f ][1,4]-thiazepine), in human plasma and post-mortem blood and tissue samples. After simple liquid-liquid extraction at pH 9.5 with n -hexane/dichloromethane (85/15, v/v), clotiapine was quantitated by HPLC-DAD and by GC-NPD. The calibration curve was linear between 10 and 1000μg/L. The limit of detection (LOD) and the limit of quantification (LOQ) were found to be 2 and 6μg/L for the GC-NPD method and 5 and 15μg/L for the HPLC-method, respectively. These methods were applied to 12 plasma samples from patients treated with clotiapine, to seven autopsy cases and to one case of driving under the influence of drugs (DUID). Concentrations ranged for the clotiapine-treated patients between 6 and 155μg/L (mean 46μg/L), and for the autopsy cases between 22 and 341μg/L (mean 123μg/L).