Losartan

A simple, rapid, and precise RP-HPLC method for simultaneous analysis of Losartan potassium and Atorvastatin calcium in bulk and its pharmaceutical formulations has been developed and validated. Atorvastatin was separated from losartan by using Grace Smart Altima C-18 column (25 cm × 4.6 mm, 5-μm) with a mobile phase consisting of acetonitrile: 10mM phosphate buffer (55:45 %v/v, pH 3.0) a flow rate of 1mL/min and detection wavelength at 240 nm. Aceclofenac was used as an internal standard in this method. Losartan, atorvastatin and aceclofenac were eluted with retention times of 4.85 min, 8.31min and 9.51 min respectively. The method was validated for accuracy, precision, linearity and sensitivity in accordance with ICH (Q2B) guidelines and the results of all the validation parameters were found to be within the acceptable limits. The calibration plots were linear over the concentration ranges from 200-30000ng/mL (r2 = 0.999) for both the drugs. Accuracy and precision were determined by QC sample covering low, medium, and high concentration levels. Intra and inert-day accuracy were found to be 97.16-102.57% for losartan and 97.01-103.05% for atorvastatin. The limit of quantification was found to be166ng/mL and 179ng/mL for losartan and atorvastain respectively. The method was successfully applied for the assay of the dosage form, recovery of the individual drugs from the combined tablet dosage was found to be >97% for both the drugs. From the results it is suggested that the proposed method is simple, reproducible, accurate and precise.

  The aim of this study was to evaluate the bioequivalence of test and reference losartan potassium 50 mg formulations in healthy volunteers. This open label, balanced, single-dose, randomized, 2-period, crossover oral bioequivalence study was conducted in 54 healthy human adult subjects under fasting condition. Subjects received losartan 50 mg of either test or reference formulation with a washout period of 7 days. After study drug administration, serial blood samples were collected over a period of 48 hours. The plasma concentrations of losartan and its active metabolite were determined by a validated method using LC/MS/MS. Pharmacokinetic parameters Cmax, Tmax, t1/2, AUC0-t, AUC 0-∞, and kel, were determined for both the  formulations. The formulations were to be considered bioequivalent if the log-transformed ratios of Cmax, AUC0-t, and AUC0-∞ were within the predetermined bioequivalence range of 80% to 125%. A total of 54 subjects were enrolled. No significant differences were found based on analysis of variance.  The mean values and 90% confidence intervals (CI) of test/reference ratios for these parameters of losartan as follows: Cmax 274.90 Vs 286.93 ng/mL (83.95 -113.69); AUC0-t 434.67 Vs 438.68 ng.hr/mL (93.30 -104.03); and AUC0-∞ 463.23 Vs 464.71 ng.hr/mL (94.65 -104.80) and for its active metabolite (losartan carboxylic acid) the mean values and 90% CI of test/reference ratios for these parameters  as follows: Cmax 572.63 Vs 543.82 ng/mL (96.87-109.37); AUC0-t 3987.89 Vs 4051.07 ng.hr/mL (93.48-104.22); and AUC0-∞ 4215.58 Vs 4271.67 ng.hr/mL (94.84-105.26). This study shows that the test formulation is bioequivalent to the reference formulation for losartan and its main active metabolite.   Key Words: Bioequivalence, Losartan, losartan carboxylic acid, Pharmacokinetics.