Quality-by-Design Based Development and Validation of Stability Indicating Method by UPLC Method for Impurities of Simvastatin from Drug and Pharmaceutical Dosage Form

Abstract

A rapid, robust and accurate ultra-high performance liquid chromatographic method was developed and validated for determination of impurities of simvastatin in drug and its pharmaceutical formulation. A systematic Quality-by-design approach was used for method development with the Fusion AETM software, to screen and optimize the column, mobile phase, column temperature, gradient time and other chromatographic conditions. The optimized method uses Waters Acquity Charged Surface Hybrid, Octadecylsilane C18 (1.7μm×2.1 mm×100 mm) column with gradient elution. Orthophosphoric acid pH was adjusted to 4.5 with triethylamine and acetonitrile with a ratio of (80:20) was used as mobile phase A, whereas methanol:acetonitrile (20:80) as mobile phase B, with a flow rate of 0.35 ml/min. Ultra Violet detector was programmed at 238 nm with a runtime of 13 min, wherein all the impurities were well resolved and were separated from main peak of simvastatin. The method was validated for accuracy, repeatability, reproducibility and robustness. All the validation parameters were in acceptable range. The linearity, limit of detection and limit of quantitation was established for all the impurities and for simvastatin. The method was also applied suitably for determining the degradation products of simvastatin using stress degradation studies