HPLC-MS/MS法快速测定人血浆中氟哌噻吨浓度及生物等效性研究  

Rapid determination of flupentixol in plasma by HPLC-MS/MS and its bioequivalence

作　　者：谭献文[1] 廖日房[2] 温预关[3] 

机构地区：[1]广东省广州市第一人民医院药剂科,510180 [2]中山大学附属第二医院药剂科 [3]广州市脑科医院国家药品临床研究基地

出　　处：《中国现代医药杂志》2009年第5期1-4,共4页Modern Medicine Journal of China

基　　金：广东省自然科学研究基金资助项目(编号:8151037001000001)

摘　　要：目的建立测定人血浆中氟哌噻吨浓度的高效液相串联质谱法(HPLC-MS/MS),用于氟哌噻吨美利曲辛片的生物等效性研究。方法以Agilent ZORBAX Eclipse Plus C18(4.6mm×150mm,5μm)为色谱柱,流动相为乙腈(含1%甲酸):0.02mol/L甲酸铵水溶液(80:20,V:V),流速:0.8ml/min;柱温:40℃,以醋酸乙酯:二氯甲烷(4:1,V:V)为提取剂。样品经电喷雾离子源正离子化后,通过三重四级杆串联质谱仪,采用选择性反应监测(SRM)对氟哌噻吨(m/z435.2→305.1)和氯普噻吨(m/z316.2→231.1)进行测定。结果氟哌噻吨的高(1μg/L)、中(0.5μg/L)、低(0.05μg/L)3个浓度的平均回收率分别为101.01%、96.19%和106.63%,日内(n=5)、日间(n=3)RSD均小于15%;分析方法的最低定量限为0.025μg/L。线性范围为:0.025～2.5μg/L,回归方程为:F=0.6625ρ+0.0049,r=0.997(n=7),权重为1/ρ2。结论该方法灵敏、准确、简单、快速,可用于临床血浓监测和药动学研究。Objective To develop a HPLC-MS/MS method for flupentixol assay in plasma,and to determine its bioequivalence. Methods Flupentixol was extracted with ethyl acetate-dichloromethane.The residues were analyzed with a HPLC-MS/MS system （Agilent ZORBAX Eclipse Plus C18,4.6mm-150mm,5μm） with the mobile phase consisted of aeetonitrile （1% formic acid） with 0.02mol/L ammonium formate （80：20,V：V）.Agilent 6410 triple quad mass spectrometer system equipped with an eleetrospray ionization ion-trap source was used as the detector and operated in the positive ion mode.Selected reaction monitoring （SRM） using the precursor to product ion combinations of m/z 435.2→305.1 and m/z 316.2→231.1 was performed to detect flupentixol and the internal standard, respectively. Results The average recoveries for flupentixol were 101.01%,96.19% and 106.63%,respectively.The within-day（n=5） and between-day（n=3） precision of variation was less than 15%.The calibration curves for flupentixol had good linearity,r=0.997 （n=7）,over the range of 0.025-2.5μg/L.The limits of quantitation for flupentixol was 0.025μg/L. Conclusion The method provides a sensitive,accurate,precise and reliable analytical procedure for clinical monitoring of flupentixol plasma and its phamacokinetic studies.

关 键 词：氟哌噻吨 血药浓度 高效液相串联质谱法 

分 类 号：R96[医药卫生—药理学]