title: Simultaneous quantification of olanzapine and its metabolite N-desmethylolanzapine in human plasma by liquid chromatography tandem mass spectrometry for therapeutic drug monitoring.
abstract: A simple, sensitive, and selective liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of olanzapine (OLZ) and its metabolite N-desmethylolanzapine (DMO) in human plasma for therapeutic drug monitoring. Sample preparation was performed by one-step protein precipitation with methanol. The analytes were chromatographed on a reversed-phase YMC-ODS-AQ C18 Column (2.0 × 100 mm,3 µm) by a gradient program at a flow rate of 0.30 mL/min. Quantification was performed on a triple quadrupole tandem mass spectrometer via electrospray ionization in positive ion mode. The method was validated for selectivity, linearity, accuracy, precision, matrix effect, recovery and stability. The calibration curve was linear over the concentration range 0.2-120 ng/mL for OLZ and 0.5-50 ng/mL for DMO. Intra- and interday precisions for OLZ and DMO were <11.29%, and the accuracy ranged from 95.23 to 113.16%. The developed method was subsequently applied to therapeutic drug monitoring for psychiatric patients receiving therapy of OLZ tablets. The method seems to be suitable for therapeutic drug monitoring of patients undergoing therapy with OLZ and might contribute to prediction of the risk of adverse reactions.
authors.affiliation: Division of Clinical Pharmacology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Hong-gang
authors.initials: HG
authors.lastname: Lou
authors.forename: Zou-rong
authors.initials: ZR
authors.lastname: Ruan
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.forename: Jin-liang
authors.initials: JL
authors.lastname: Chen
mesh_terms: D000328:Adult; D001569:Benzodiazepines / Q000097:blood* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000097:blood; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
chemical_list: D001569:Benzodiazepines; D010890:Pirenzepine; C425329:desmethylolanzapine; D000077152:Olanzapine
keywords: LC-MS/MS; N-desmethylolanzapine; olanzapine; therapeutic drug monitoring