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, CAPCELL PAK C18 MG��(2.0 mm��50 mm, 5 ��m) 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 (20��80) 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 10.10-2 525 ng��mL-1 for losartan potassium and 9.820-2 455 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.
WANG Yan-Ran-,
WANG Cai-Ping-,
XIE Hui-Ru- etc
.Simultaneous HPLC-MS/MS Determination of Losartan Potassium and Its Metabolite E-3174 in Human Plasma and Its Application to Pharmacokinetic Study[J] Chinese Pharmaceutical Journal, 2014,V49(12): 1056-1061
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2014, Vol. 49 
