Lou Hong-gang, Ruan Zou-rong, Jiang Bo, Chen Jin-liang
Division of Clinical Pharmacology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Biomed Chromatogr. 2015 May;29(5):671-8. doi: 10.1002/bmc.3329. Epub 2014 Oct 8.
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.
建立了一种简单、灵敏且具选择性的液相色谱串联质谱法（LC-MS/MS），用于同时定量测定人血浆中的奥氮平（OLZ）及其代谢物N-去甲基奥氮平（DMO），以进行治疗药物监测。样品制备采用甲醇一步蛋白沉淀法。分析物在反相YMC-ODS-AQ C18柱（2.0×100 mm，3 µm）上通过梯度洗脱程序进行色谱分离，流速为0.30 mL/min。在三重四极杆串联质谱仪上通过电喷雾电离在正离子模式下进行定量分析。该方法在选择性、线性、准确度、精密度、基质效应、回收率和稳定性方面均经过验证。奥氮平的校准曲线在0.2-120 ng/mL浓度范围内呈线性，N-去甲基奥氮平的校准曲线在0.5-50 ng/mL浓度范围内呈线性。奥氮平和N-去甲基奥氮平的日内和日间精密度均<11.29%，准确度范围为95.23%至113.16%。随后将所建立的方法应用于接受奥氮平片治疗的精神科患者的治疗药物监测。该方法似乎适用于接受奥氮平治疗患者的治疗药物监测，可能有助于预测不良反应风险。
