Simultaneous determination of ezetimibe and simvastatin in rat plasma by stable-isotope dilution LC-ESI-MS/MS and its application to a pharmacokinetic study

作     者：Sireesha R.Karanam Prakash Katakam Babu R.Chandu Nagiat T.Hwisa Shanta K.Adiki 

作者机构：Vimta Life SciencesAlexandria Knowledge ParkGenome ValleyHyderabadAPIndia Faculty of PharmacyUniversity of ZawiaAl-ZawiyaLibya Nirmala College of PharmacyGunturIndia 

出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)

年 卷 期：2014年第4卷第4期

页      面：286-294页

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

主　　题：Ezetimibe Simvastatin PharmacokineticsRat plasma LC-ESI-MS/MS 

摘      要：A simple, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed for simultaneous quantification of ezetimibe and simvastatin in rat plasma. The deuterium isotopes： ezetimibe d4 and simvastatin d6 were used as internal standards for ezetimibe and simvastatin, respectively. MS/MS detection involved a switch of electron spray ionization mode from negative to positive at retention time 3.01 rain. Samples were extracted from plasma by liquid-liquid extraction using tertiary butyl methyl ether. Chromatographic separation was achieved with Agilent Eclipse XBD-CIs column using mobile phase that consisted of a mixture of ammonium acetate （pH4.5; 10 mM）-acetonitrile （25：75 v/v）. The method was linear and validated over the concentration range of 0.2--40.0 ng/rnL for simvastatin and 0.05-15.0 ng/mL for ezetimibe. The transitions selected were m/z 408.3→271.1 and m/z 412.0→275.10 for ezetimibe and ezetimibe d4, and m/z 419.30 → 285.20 and rrdz 425.40 →199.20 for simvastatin and simvastatin d6. Intra- and inter-batch precisions for ezetimibe were 1.6-14.8% and 2.1-13.4%; and for simvastatin 0.94-9.56% and 0.79-12%, respectively. The proposed method was sensitive, selective, precise and accurate for the quantification of ezetimibe and simvastatin simultaneously in rat plasma. The method was successfully applied to a pharmacokinetic study by oral co-administration of ezetimibe and simvastatin in SD rats.