Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma by LC-MS/MS and bioequivalence study of irbesartan hydrochlorothiazide tablet
10.13699/j.cnki.1001-6821.2018.07.037
- VernacularTitle: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
- Author:
Wei-Dong ZHANG
1
;
Yun-Hao ZHANG
;
Yu-Qin HU
Author Information
1. 河北医科大学公共卫生学院
- Keywords:
irbesartan;
hydrochlorothiazide;
LC-MS/MS;
bioequivalence
- From:
The Chinese Journal of Clinical Pharmacology
2018;34(7):861-865
- CountryChina
- Language:Chinese
-
Abstract:
Objective To develop a method for simultaneous determination of irbesartan and hydrochlorothiazide in human plasma by LC-MS/MS,and to evaluate bioequinalence of 2 kinds of irbesartan hydrochlorothiazide tablets in healthy volunteers.Methods Using losartan potassium as internal standard,the plasma samples were extracted with solid phase extraction (SPE).The Agilent Zorbax SB-C1s column (1.8 μm,4.6 mm × 50 mm) was used,the mobile phase consisted of methanol-acetonitrile-0.15％ methanoic acid solution (40∶ 25∶35),flow rate was 0.3 mL · 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 investigated.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 were y =9.28 × 10-2x-7.50 × 10-2 (r =0.999 2) for irbesartan and y =5.27 × 10-2x-2.99 × 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.
