Simultaneous quantification of related substances of ezetimibe and simvastatin in combined dosage form using a novel stability-indicating liquid chromatographic method

Abstract

A novel, simple, robust, and rapid reversed-phased high-performance liquid chromatographic method has been developed for the separation and quantitative determination of the related substances of ezetimibe and simvastatin in combined dosage forms. Successful separation of the drug from the process-related impurities and degradation products formed under stress conditions was achieved on Inertsil ODS-3V (150 × 4.6 mm, 5.0 μm) column. The gradient liquid chromatography (LC) method employs solution A and solution B as mobile phase. The solution A contains 0.1% orthophosphoric acid solution in water, and solution B contains 0.1% orthophosphoric acid solution in acetonitrile. Flow rate was monitored at 2.0 mL/min, and the ultraviolet (UV) detection, at 238 nm. In forced degradation studies, the effect of acid, base, oxidation, UV light, and temperature was investigated, showing that good resolution between the peaks corresponds to process-related impurities and degradation products from both analyte. The performance of the method was validated according to the present International Conference on Harmonization (ICH) guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, ruggedness, and robustness. To the best of our knowledge, a rapid LC method, which separates all the impurities of ezetimibe and simvastatin in combined dosage forms, disclosed in this investigation was not published elsewhere.

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

“…The degradation behavior studies using ultra-high performance liquid chromatography (UHPLC)/Mass spectrometry (MS) is reported [1] . There are various stability indicating methods available for determination of SMV along with the other drugs and its degradation products [13][14][15][16][17] . But these methods are either non-specific with respect to Pharmacopoeial impurities or having very long run time.…”