A validated RP-HPLC method for the determination of rosuvastatin in presence of sacubitril/valsartan in rat plasma: Application to in vivo evaluation of OATP-mediated drug interaction potential between rosuvastatin and sacubitril/valsartan

Publication date: Available online 19 July 2018Source: Microchemical JournalAuthor(s): Bahia Abbas Moussa, Hanaa M.A. Hashem, Marianne Alphonse Mahrouse, Sally Tarek MahmoudAbstractEntresto® tablets (sacubitril/valsartan combination) were recently approved by FDA to reduce the risk of cardiovascular death in patients with chronic heart failure. Entresto® is usually administered in conjunction with rosuvastatin. Sacubitril inhibits organic anion-transporting polypeptides (OATP) responsible for the uptake of rosuvastatin into human hepatocytes. The aim of this investigation was to evaluate OATP-mediated drug interaction potential between rosuvastatin and sacubitril/valsartan upon co-administration in rats. An RP-HPLC method was developed and validated for determination of rosuvastatin in rat plasma in presence of sacubitril and valsartan. A Zorbax Eclipse C18 Cyano column was used as stationary phase and acidified water (pH 3, adjusted with acetic acid): acetonitrile (55: 45, v/v) as mobile phase at flow rate 1 ml/min, using UV detection at λ 254 nm. Liquid–liquid extraction was applied for drug extraction from plasma, using diethyl ether: dichloromethane (70: 30, v/v). The method was linear over concentration range of 2–200 μg/ml. Coefficient of variation ranged from 0.033 to 3.5% and 0.329 to 3.92% for intraday and interday precision, respectively. The accuracy values were found to be between 95.4 and 101.71%. The method was successfully applied to in vivo pha...
Source: Microchemical Journal - Category: Chemistry Source Type: research