DEVELOPMENT OF THE G C -M S /M S METHOD FOR QUALITATIVE AND QUANTITATIVE DETERMINATION OF CLOZAPINE IN HUMAN BLOOD.

A simple, rapid, selective, sensitive gas chromatography-mass spectrometry (GC-MS/MS) method was developed and validated for the determination of clozapine in human blood. For isolation was used solid phase extraction. The calibration standards range was 5-1500ng/mL. Analysis was carried out on a gas chromatograph Agilent 7000A Quadrupole GC-MS/MS. GC run conditions - capillary column HP-5MS, 30m × 0.25mm, coated with a 0.25μm film, column temperature from 50°C to 305°C with an increase of 10°C/min; the injection port and the transfer line temperature were 310°C; carrier gas - helium at flow rate of 1.0 mL/min; Ionization was performed in the positive mode (EI+). Acquisition was made in TIC and MRM mode, electron impact 70Ev. Quantitative analysis was carried out by recording ions m/z 326 → 256, m/z 326 → 243 and m/z 326 → 192 for clozapine. The method was validated by investigating the following parameters: selectivity, linearity, accuracy, precision, identification of LOD and LLOQ and recovery. Method, given in this paper can be useful for determination of clozapine in forensic investigations and for TDM of schizophrenic patients to improve therapeutic efficacy during clozapine treatment.