| DOI: 10.29090/psa.2018.04.018.0012
| Pharm Sci Asia 2018; 45(4), 252-262 |
Liquid chromatography tandem mass spectrometry method for simultaneous determination of losartan and its active metabolite in human plasma Jureeporn Sri-in1, Jedsadaporn Prakobkijcharoen1, Wannisa Thanakosai1, Somruedee Chatsiricharoenkul1, Weerawadee Chandranipapongse1*
- Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
A highly selective, sensitive and reproducible liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of losartan and its active metabolite (EXP3174) in human plasma, using candesartan as an internal standard (IS), was described. Chromatographic separation was carried out in the Luna HST 2.5μm C18 (50x3 mm.). The mobile phases were 0.05% formic acid and acetonitrile at a ratio of 3.3:6.7 (v/v). The mass spectrometry was operated in positive electrospray ionization and multiple reactions monitoring (MRM) mode. Liquidliquid extraction (LLE) was employed with the mixture of ethylacetate and hexane at a ratio of 9:1 (v/v). The method was developed and fully validated according to the USFDA guidance. The limit of detection (LOD) of losartan and EXP3174 were 0.10 and 0.20 ng/mL, respectively and the lower limit of quantification (LLOQ) of both losartan and EXP3174 were 0.5 ng/mL. This method demonstrated good linearity (r2>0.999) ranged from 0.52,500 ng/mL for both losartan and EXP3174. Accuracy and precision of the method were acceptable with high recovery of extraction. Neither anticoagulant nor matrix affected the analysis. This method was successfully applied to determine the concentrations of losartan and EXP3174 in human plasma in a bioequivalence study.
Keyword:
LC-MS/MS; Losartan; EXP3174; Candesartan; Liquid-liquid extraction
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