HPLC-MS/MS同时测定人体血浆中氯沙坦钾与其代谢物氯沙坦羧酸(E-3174)的浓度及其药动学应用  

Simultaneous HPLC-MS /MS Determination of Losartan Potassium and Its Metabolite E-3174 in Human Plasma and Its Application to Pharmacokinetic Study

作　　者：王嫣然[1] 王彩平 谢荟茹[1] 王凌[1] 蒋学华[1] 

机构地区：[1]四川大学华西药学院,成都610041 [2]北京万生药业有限责任公司,北京100022

出　　处：《中国药学杂志》2014年第12期1056-1061,共6页Chinese Pharmaceutical Journal

摘　　要：目的建立灵敏、快速的液相色谱串联质谱法测定人血浆中氯沙坦钾和氯沙坦羧酸（E-3174）浓度。方法血浆样品中加入适量内标和冰乙酸，以叔丁基甲醚萃取后用API3000LC—MS／MS进行分析。色谱柱采用SHISEIDO，CAPCELLPAKC18 MGⅡ（2．0mmX50mm，5μm），柱温为室温，流动相由0．1％甲酸水溶液（含5mmol·L-1^醋酸铵）-乙腈（含0．1％甲酸）（20：80）组成，流速0．85mL·min-1^。质谱采用多反应离子监测（MRM）的扫描模式，以电喷雾离子源（ESI）在正离子电离模式下进行测定。结果本方法的线性范围是10．10—2525ng·mL-1^（氯沙坦钾）和9．820～2455ng·mL-1^（E-3174），最低定量限为10．10ng·mL-1^（氯沙坦钾）和9．820ng·mL-1^（E-3174），日内、日间精密度均小于9．22％，准确度在93．56％～102．88％之间，萃取回收率约70％，稳定性考察结果良好，单个样品分析时间仅为2．5min。2种制剂的相对生物利用度为96．5％（氯沙坦钾）、110．0％（E-3174）。不同来源的2种氯沙坦钾片具有生物等效性。结论本方法快速、灵敏、专属性强，适用于氯沙坦钾的人体药动学研究及其制剂的生物等效性研究。OBJECTIVE To develop a sensitive and rapid HPLC-MS/MS method for the determination of losartan potassium and E-3174 in human plasma. METHODS The plasma samples were extracted with methyl tert-butyl ether （MTBE） after addition of in- ternal standard and acetic acid, and then analyzed with API 3000 LC-MS/MS system. The analytical column was SHISEIDO, CAP- CELL PAK Ct8 MG ]] （2.0 mm ×50 mm,5μm） and the column temperature was room temperature. The mobile phase was composed of 0. 1% formic acid in water （containing 5 mmol · L-1^ ammonium acetate） -0. 1% formic acid in acetonitrile （20： 80） and the flow rate was 0. 85 mL · min -1^. Detection was performed with multiple reactions monitoring （MRM） using positive electrospray ionization （ESI）. RESULTS The calibration curves were linear over the concentration ranges of 10. 10 -2 525 ng· mL-1^ for losartan potassi- um and 9. 820 -2 455 ng - mL-1^ for E-3174, respectively. The lower-limit-of-quantifications were 10. 10 ng · mLi for losartan potas- sium and 9. 820 ng · mL-1^ for E-3174, respectively. Inter- and intra-day precisions were less than 9.22% and accuracy was within 93.56% - 102. 88%. Extraction recoveries were around 70% and the analytes were proved to be stable. Total run time of an analyte was only 2. 5 rain. The relative bioavailabilities of the two preparations were 96. 5% for losartan potassium and 110. 0% for E-3174. These two losartan potassium preparations were bioequivalent. CONCLUSION This method is rapid, sensitive, specific and applica- ble to the pharmacokinetic study in human and bioequivalence study of losartan potassium.

关 键 词：液相色谱质谱联用 氯沙坦钾 E-3174 药动学 生物等效性 

分 类 号：R285[医药卫生—中药学]