LC-MS/MS法测定人体氟桂利嗪浓度及生物等效性评价应用  

LC-MS/MS determination of flunarizine in human plasma and application in bioequivalence evaluation

作　　者：陈尧[1] 谭志荣[1] 王医成[1] 李慧[1] 李玲[1] 邓晓兰[1] 张伟[1] 周宏灏[1] 

机构地区：[1]中南大学临床药理研究所湖南省遗传药理学重点实验室

出　　处：《中国临床药理学与治疗学》2011年第4期400-406,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：中央高校基本科研业务青年教师助推项目(201012200047)

摘　　要：目的：建立LC-MS/MS法测定人体血浆氟桂利嗪的浓度,并研究由扬子江药业集团有限公司生产的盐酸氟桂利嗪滴丸的相对生物利用度。方法：色谱柱为Thermo Hypurity C18（150 mm×2.1 mm,5μm）,流动相为乙腈-10 mmol/L甲酸铵（含0.1%甲酸）（65∶35,V/V）;流速：0.3 mL/min;进样量：10μL;柱温：40℃,样品室温度为15℃。采用双周期随机交叉试验设计。分别给予18名男性健康受试者试验制剂或参比制剂氟桂利嗪20 mg,采用LC-MS/MS法测定给药后不同时间的血药浓度。结果：氟桂利嗪线性范围为0.38-196 ng/mL,氟桂利嗪最低检测限为0.1 ng/mL,方法灵敏、稳定、特异性高。试验制剂与参比制剂的主要药代动力学参数Cmax、tmax、AUC0-24和AUC0-∞分别为：（86±36）和（82±34）ng/mL、2.5 h（1-3 h）和3 h（2~5 h）、（725±338）和（709±320）ng.mL-1.h、（811±375）和（780±330）ng.mL-1.h。氟桂利嗪受试制剂与参比制剂具有生物等效性。结论：该方法简便、准确、重复性好,并成功地应用到人体盐酸氟桂利嗪生物等效性评价。AIM： To establish a LC-MS/MS method for determination of flunarizine in human plasma,and to study the relative bioequivalence of flunarizine hydrochloride made by Yangtze River Pharmaceutical Group Co.,Ltd. METHODS： Thermo Hypurity C18 column（150 mm×2.1 mm,5 μm） was used in the experiment.Acetonitrile-10 mmol/L ammonium formate（including 0.1% formic acid）（65∶35,V/V） was used as mobile phase and the flow rate was 0.3 mL/min and the injection volume was 10 μL.The column temperature was set at 40 ℃,the sample room temperature was set at 15℃.A single oral dose of 20 mg flunarizine hydrochloride and its contrastive drug were given to 18 healthy volunteers in an open randomized two way crossover design.The plasma concentrations were determined by LC-MS/MS method at the different time points.RESULTS：Flunarizine was linear in the range of 0.38-196 ng/mL,the limitation of detection for flunarizine was 0.1 ng/mL,the method was high sensitivity,stability and specificity.The main pharmacokinetic parameters of flunarizine were as follows： Cmax was（86±36） and（82±34）ng/mL;tmax was 2.5 h（1-3 h） and 3 h（2-5 h）;AUC0-24 was（725±338） and（709±320） ng·mL-1·h;AUC0-∞ was（811±375） and（780±330） ng·mL-1·h.The reference drug and the test drug of flunarizine are bioequivalent.CONCLUSION： The method is simple,accurate and repetitive for the determination of flunarizine in human plasma and successfully applied to the bioequivalence evaluation of flunarizine hydrochloride in human.

关 键 词：氟桂利嗪 LC-MS/MS 药代动力学 

分 类 号：R969.1[医药卫生—药理学] R917[医药卫生—药学]