Search

Objective: To develop a method to measure trihexyphenidyl, chlorpromazine and clozapine in human blood with GC-MS., Methods: The specimens were alkalized (pH > 10) and extracted with V (benzene):V(ethyl acetate) = 1:1, and qualitatively analyzed using GC-MS-Full Scan with internal standard SKF525A. The specimens were alkalized (pH > 10) and extracted with V(benzene):V(ethyl acetate) = 1:1, and quantitatively analyzed using GC-MS-SIM with internal standard diazepam-d5., Results: The lowest detection limits of trihexyphenidyl, chlorpromazine and clozapine were 0.3, 0.3 and 0.7 ng/mL (S/N > or = 3) respectively. The calibration curve in 20-10 000 ng/mL showed a good linear distribution. The recovery rate was 79.9% to 85.5%. The RSDs of intraday and interday were less than 5.1%., Conclusion: The established method was simple, sensitive and accurate for simultaneous determination of trihexyphenidyl, chlorpromazine and clozapine in human blood, and can be applied in forensic toxicological cases.

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 x 150 mm, 5 microm). 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 10.0-2000.0 ng/mL showed a good linear distribution (r > or = 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.

This article reports a highly sensitive method specific for determination of clozapine(CLP) and its N-demethylated metabolite (DCLP) in serum by gas chromatography-mass spectrometry with selected ion monitoring. A 0.5 mL serum was alkalized with 0.5 mL 1.0 mol/L sodium hydroxide and was extracted with 5 mL ether, then the organic phase was transferred to another tube containing 1 mL 0.1 mol/L hydrochloric acid. After being shaken and centrifuged, the organic phase was discarded, and 10 microL 100 micrograms/L diazepam (DAP) was added to the water phase as internal standard, then 0.5 mL 1.0 mol/L sodium hydroxide and 5 mL ether were added. The extract was evaporated to dryness and then was acylated with 50 microL trifluoroacetic anhydride under 50 degrees C for 45 min. The excess of the reagent was evaporated and the residue was disolved in 20 microL acetone. Take 2 microL for gas chromatography-mass spectrometry analysis. Chromatographic conditions were: column DB-1 (30 m x 0.25 mm x 0.25 microns), injector 260 degrees C, interface 250 degrees C, column oven with temperature program: [equation: see text] Helium carrier gas flow rate was 1.8 mL/min. The mass spectrometer was adjustd to record the ion m/z352 for CLP and DCLP, and m/z 256 for DAP in quantitation. The minimum detection limits were 0.1 microgram/L for CLP and 0.2 microgram/L for DCLP. The standard curves of CLP and DCLP were linear between 1-128 micrograms/L (rCLP = 0.998, rDCLP = 0.999). Recoveries of two substances were better than 83%, and the RSD values were less than 10%. This method has been successfully used in clinical pharmacokinetic study of CLP before and after CYP1A2 inhibitor used. The results indicate that the metabolism of clozapine is strongly affected by CYP1A2 activity.