Development and validation of a hydrophilic interaction liquid chromatography method for the quantitation of impurities in fixed-dose combination tablets containing rosuvastatin and metformin.

A hydrophilic interaction liquid chromatography method with diode array detection (HILIC-DAD) was developed and validated for the simultaneous determination of impurities in extended-release fixed-dose combination tablets containing rosuvastatin and metformin in a ratio 1:100. The analytes were separated by hydrophilic interaction liquid chromatography using an XBridge®-HILIC analytical column under isocratic elution. The mobile phase was composed of ammonium formate at 150 mM containing 0.05% diethylamine (pH 8.5)/acetonitrile, 4/96 (v/v) and pumped at a flow rate of 0.5 mL min-1 . Method validation was performed according to ICH guidelines. The calibration curves for rosuvastatin, metformin and their seven impurities showed good linearity (r > 0.994) within the calibration ranges tested. The intra- and inter-day R.S.D. values were less than 4.5%, while the relative percentage error Er was less than 2.7% for all compounds. Accelerated stability studies performed under various stress conditions including hydrolysis, oxidation and heat proved the selectivity of the procedure. A run time of less than 25 min for each sample made it possible to analyze a large number of samples per day. The method is the first reported application of HILIC for the analysis of impurities in fixed-dose combination tablets containing rosuvastatin and metformin and it can be used for the quality control of these drugs.