LC-MS/MS法同时测定厄贝沙坦和氢氯噻嗪血药浓度及厄贝沙坦氢氯噻嗪片的生物等效性研究  

Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma by LC-MS/MS and bioequivalence study of irbesartan hydrochlorothiazide tablet

作　　者：张伟东[1,2] 张运好[3] 胡玉钦[3] ZHANG Wei - dong1＇2, ZHANG Yun - hao3, HU Yu - qin3(1. School of Public Health, Hebei Medical University, Shijiazhuang 050017, China; 2. Department of Pharmacy, The First Hospital of Qinhuangdao , Qinhuangdao 066000, Hebei Province, China; 3. Department of Pharmacy, Bethune International Peace Hospital, Shijiazhuang 050382, Chin)

机构地区：[1]河北医科大学公共卫生学院,石家庄050017 [2]秦皇岛市第一医院药学部,河北秦皇岛066000 [3]白求恩国际和平医院药剂科,石家庄050082

出　　处：《中国临床药理学杂志》2018年第7期861-865,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家科技重大专项"重大新药创制"基金资助项目(2011ZXJ09202-012)

摘　　要：目的建立同时测定人血浆中厄贝沙坦和氢氯噻嗪血药浓度的液相色谱-质谱方法,并评价2种厄贝沙坦氢氯噻嗪片的生物等效性。方法以氯沙坦为内标,血浆样品经固相萃取后检测。Agilent Zorbax SB-C18(4.6 mm×50mm,1.8μm)为分析柱,以甲醇-乙腈-0.15%甲酸水溶液(40∶25∶35)为流动相,流速:0.3 m L·min^(-1),用电喷雾离子化源(ESI),以负离子多离子反应监测(MRM)扫描方式进行监测。22例健康男性受试者随机于2个周期交叉口服相同剂量的厄贝沙坦氢氯噻嗪片受试药物或参比药物,考察其生物等效性。结果血浆中厄贝沙坦和氢氯噻嗪浓度分别在20.0~4000.0 ng·m L^(-1)和1.0~200.0 ng·m L^(-1)线性关系良好,线性回归方程分别为y=9.28×10^(-2)x-7.50×10^(-2)(r=0.999 2)和y=5.27×10-2x-2.99×10-2(r=0.998 8),日内和日间RSD均小于15%。受试药物相对于参比药物的厄贝沙坦和氢氯噻嗪的生物利用度分别为(107.4±19.9)%和(105.6±16.2)%。结论本方法简便、快速、灵敏度高,适用于人血浆中厄贝沙坦、氢氯噻嗪的浓度测定,可用于厄贝沙坦氢氯噻嗪片的人体生物等效性研究;2种药物生物等效。Objective To develop a method for simultaneous determina- tion of irbesartan and hydrochlorothiazide in human plasma by LC - MS/ MS, and to evaluate bioequinalence of 2 kinds of irbesartan hydrochlo- rothiazide tablets in healthy volunteers. Methods Using losartan potas- sium as internal standard, the plasma samples were extracted with solid phase extraction （SPE）. The Agilent Zorbax SB -C18 column （1.8 μm, 4. 6 mm x 50 ram） was used, the mobile phase consisted of methanol - acetonitrile -0. 15% methanoic acid solution （40： 25：35） , flow rate was 0.3 m L·min-1. Electrospray ionization （ESI） source was applied and operated in negative multiple reactions monitoring （MRM） mode. In a randomized two - periods cross - over study, the bioequivalence of test preparation and reference preparation of irbesartan hydrochlorothiazide tablets in 22 healthy male volunteers after oral administration were inves- tigated. Results The calibration curves were linear within the range of 20. 0 - 4000.0 ng· mL- 1 for irbesartan and 1.0 - 200. 0 ng· mL- 1 for hydrochlorothiazide in human plasma, the linear regression equation werey = 9.28 x10 -2x - 7.50 x 10 -2 （ r = 0. 999 2） for irbesartan and y = 5.27 x 10 -2x - 2.99 x 10 -2 （ r = 0. 998 8 ） for hydrochlorothiazide, respectively. The relative standard deviation （RSD） of intra and inter precision were less than 15% for both irbesartan and hydrochlorothiazide. The relative bioavailabilities of irbesartan and hydrochlorothiazide of compound tablets were （ 107.4 ± 19.9） % and （ 105.6 ± 16. 2） %, respectively. Conclusion The method is simple, fast and sensitive, and it is suitable for the plasma concentration determination and bioequinalence study of irbesartan hydrochlorothiazide tablets in healthy volunteers. Two preparations are bioequivalent.

关 键 词：厄贝沙坦 氢氯噻嗪 液相色谱-质谱 生物等效性 

分 类 号：R972[医药卫生—药品]