Simultaneous HPLC-MS/MS determination of losartan potassium and its metabolite E-3174 in human plasma and its application to pharmacokinetic study / 中国药学杂志

ABSTRACT

OBJECTIVE: To develop a sensitive and rapid HPLC-MS/MS method for the determination of losartan potassium and E-3174 in human plasma. METHODS: The plasma samples were extracted with methyl tert-butyl ether (MTBE) after addition of internal standard and acetic acid, and then analyzed with API 3000 LC-MS/MS system. The analytical column was SHISEIDO, CAP-CELL PAK C18 MG II (2.0 mm × 50 mm, 5 μm) and the column temperature was room temperature. The mobile phase was composed of 0.1% formic acid in water (containing 5 mmol·L-1 ammonium acetate) -0.1% formic acid in acetonitrile (2080) and the flow rate was 0.85 mL·min-1. Detection was performed with multiple reactions monitoring (MRM) using positive electrospray ionization (ESI). RESULTS: The calibration curves were linear over the concentration ranges of 10.10-2525 ng·mL-1 for losartan potassium and 9.820-2455 ng·mL-1 for E-3174, respectively. The lower-limit-of-quantifications were 10.10 ng·mL-1 for losartan potassium and 9.820 ng·mL-1 for E-3174, respectively. Inter-and intra-day precisions were less than 9.22% and accuracy was within 93.56%-102.88%. Extraction recoveries were around 70% and the analytes were proved to be stable. Total run time of an analyte was only 2.5 min. The relative bioavailabilities of the two preparations were 96.5% for losartan potassium and 110.0% for E-3174. These two losartan potassium preparations were bioequivalent. CONCLUSION: This method is rapid, sensitive, specific and applicable to the pharmacokinetic study in human and bioequivalence study of losartan potassium.