Isolation and Spectral Characterization of Degradation Impurity in Perampanel Drug Substance Using UPLC-MS and NMR Spectroscopy: Validation of Assay Method by UPLC

摘要

A stability indicating reverse phase ultra performance liquid chromatography (UPLC) for perampanel and identification of degradation products of perampanel from forced degradation studies. Perampanel was subjected to stress conditions of acid, aqueous hydrolysis, oxidative, photolytic and thermal stress degradation. The degradation of perampanel was observed under acid hydrolysis, basic hydrolysis and peroxide and it was stable in thermal, photo degradation conditions. Good resolution was observed between drug and its degradation products with the proposed UPLC method was developed by using mobile phase formic acid in water and acetonitrile. The developed UPLC method was validated with respect to specificity, linearity, accuracy, precision, ruggedness and robustness. The linearity of method was performed concentration levels between 20 to 120 ug/mL with correlation coefficient 0.999. Assay recoveries were found to be 98.2 to 101.6 %. The developed UPLC method was found to be useful to determine the regular production of perampanel samples and its stability studies. Two new degradants were formed (1-2). Both acid and base hydrolysis resulted in the same compound 1, However, oxidation by peroxide resulted in another new compound 2. Both degradation products were completely characterized by HRMS and extensive NMR, spectrometry. Stability indicating validated method by UPLC and its degradation and cartelization studies were not reported elsewhere.