摘要
目的建立同时测定人血浆中喹硫平及其磺氧化-、7-羟基-和7-羟基-氮-去烷基-代谢产物浓度的高效液相色谱-电喷雾电离质谱联用法。方法采用Kromasil C18反相柱(250 mm×4.6 mm,5μm),以水(含甲酸1.70mmol.L-1,醋酸铵5.8 mmol.L-1)-乙腈(65∶35)为流动相,流速0.95 mL.min-1。质谱采用电喷雾电离源正离子模式(ESI+),选择离子监测(SIR)各物质准分子离子峰,样品用固相萃取法处理。结果喹硫平和磺氧化喹硫平在10~2 000μg.L-1,7-羟基-喹硫平和7-羟基-氮-去烷基喹硫平在1~200μg.L-1线性关系良好,萃取回收率均>85%,方法回收率均>95%,日内、日间RSD均<15%。结论该方法专一性强、灵敏度高、简单,可用于研究喹硫平的代谢机制以及药物动力学。
OBJECTIVE To develop a high performance liquid chromatography-electrospray mass spectrometry （HPLC-MS/ESI） method for the simultaneous determination of quetiapine and its sulfoxide-, 7-hydroxy-, 7-hydroxy- N-dealkyl-metabolites in human plasma. METHODS The HPLC separation of the compounds was performed on a Kromasil Cl8 （250 min×4. 6mm, 5 μm） column, using water （formic acid： 1.70 mmol · L^-1 , ammonium acetate： 5.8 mmol·L^-1） -acetonitrile （65 ： 35） as the mobile phase, with a flow rate of 0. 95 mL· min^-1. The compounds were ionized in the electrospray ionization （ESI） ion source of the mass spectrometer and detected in the selected ion recording （SIR） mode. The samples were extracted using solid-phase extraction columns. RESULTS The calibration curves were linear in the range of 10-2 000 μg · L^-1 for quetiapine and quetiapine sulfoxide, 1-200 μg · L^-1 for 7- hydroxy-N-desalkyl-quetiapine and 7 hydroxy-quetiapine, respectively. The average extraction recoveries for all the four samples were above 85%. The methodology recoveries were much higher than 95%. The intra-day and inte-day RSD were less than 15%. CONCLUSIONS The method is accurate, sensitive, and simple for the study of pharmacokinetics and metabolic mechanism of quetiapine in patients at therapeutic doses.
出处
《中南药学》
CAS
2006年第2期88-91,共4页
Central South Pharmacy
