Abstract: Objective To develop a method for determination of clozapine, olanzapine and mirtazapine in human plasma by liquid chromatography-tandem mass spectrometry(LC-MS/MS). Methods Clozapine, olanzapine and mirtazapine were extracted from plasma samples by using diethyl ether and separated by Agilent Zorbax SB-C18 column(2.1 mm×150 mm, 5 μm). Electrospray ionization source was applied, positive ion mode was used to detect and multiple reaction monitoring mode was used to quantify clozapine, olanzapine and mirtazapine. Carbamazepine was the internal standard. Results The detection limits of clozapine, olanzapine and mirtazapine were within 0.41-0.92 ng/mL. The calibration curve in the concentration range of 10.0-2 000.0 ng/mL showed a good linear distribution (r≥0.992 4). The average extraction recoveries were within 65.7%-94.2%. Intra-day RSD and inter-day RSD were less than 6%(n=5). Conclusion This method seems to be quite specific, sensitive and accurate, and can be used to detect clozapine, olanzapine and mirtazapine in forensic and clinical analytic toxicology.

Key words: forensic toxicology, liquid chromatography-tandem mass spectrometry(LC-MS/MS), clozapine, olanzapine, mirtazapine, plasma