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

Talanta. 2018 Jun 1;183:131-141. doi: 10.1016/j.talanta.2018.02.068. Epub 2018 Feb 17.

Abstract

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.

Keywords: HILIC; Impurities; Metformin; Method development; Method validation; Rosuvastatin.

Publication types

  • Validation Study

MeSH terms

  • Chromatography, High Pressure Liquid
  • Drug Contamination*
  • Hydrophobic and Hydrophilic Interactions*
  • Metformin / analysis*
  • Rosuvastatin Calcium / analysis*
  • Tablets / analysis

Substances

  • Tablets
  • Rosuvastatin Calcium
  • Metformin