HPLC-MS/ESI法同时检测血浆中4种非典型抗精神病药物

Simultaneous determination of 4 atypical antipsychotics in the plasma by HPLC-MS/ESI

目的 建立同时测定血浆中的非典型抗精神病药利培酮、氯氮平、奥氮平和奎硫平HPLC-MS/ESI法。方法样品经碱化后用乙醚2次提取,采用NUCLEODUR C18(2.0 mm×125 mm,3μm)柱,水(甲酸:2.7 mmol·L-1,醋酸铵:10 mmol·L-1)-乙腈(53:47,v/v)为流动相,以地西泮为内标,电喷雾电离源正源(ESI+)选择离子峰检测。结果 氯氮平和奎硫平在20～1000μg·L-1内,利培酮和奥氮平在1～50μg·L-1内线性关系良好,4种药物的萃取回收率均>90％,方法回收率均>95％,日间差和日内差均<15％。结论 此方法准确、灵敏、简单,适用于这4种药物的常规治疗药物浓度监测(TDM)、药物动力学及代谢机制的研究。

OBJECTIVE To establish a sensitive method to determine clozapine, olanzapine, risperidone and que-tiapine simultaneously in the human plasma by high-performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI). METHODS The analytes were extracted twice by ether after alkalinizing the samples. HPLC separation of the analytes was performed on a NUCLEODUR C18 (2. 0 mm× 125 mm, 3 μn) column, using water (formic acid: 2. 70 mmol · L-1, ammonium acetate: 10 mmol ·μL-1) -acetonitrile (53 : 47) as the mobile phase, with a flow-rate of 0. 16 mL · min-1. The compounds were ionized in the electrospray ionization ion source of the mass spectrometer and detected in the selected ion recording mode. RESULTS The calibration curves were linear within the ranges of 20-1 000 μg · L-1 for clozapine and quetiapine, and 1-50 μg · L-1 for olanzapine and risperidone , respectively . The average extraction recoveries for the 4 analytes were higher than 90 % . The methodology recoveries were higher than 95% for the analytes. The intra-day and inter-day RSD were lower than 15%. CONCLUSIONS The method is accurate, sensitive, and simple for therapeutic drug monitoring and study of pharmacokinetics of the 4 drugs.