Analytical method development and validation for the analysis of verapamil hydrochloride and its related substances...

A novel, economic, and time-efficient stability-indicating, reverse-phase ultra-performance liquid chromatographic (RP-UPLC) method has been developed for the analysis of verapamil hydrochloride in the presence of both impurities and degradation products generated by forced degradation. When verapamil hydrochloride was subjected to acid hydrolysis, oxidative, base hydrolysis, photolytic, and thermal stress, degradation was observed only in oxidative and base hydrolysis. The drug was found to be stable to other stress conditions. Successful chromatographic separation of the drug from impurities formed during synthesis and from degradation products formed under stress conditions was achieved on a Shimpak XR ODS, 75mm×3.0mm, 1.7μ particle size column, UV detection at 278nm and a gradient elution of ammonium formate, orthophosphoric acid and acetonitrile as mobile phase. The method was validated for specificity, precision, linearity, accuracy, robustness and can be used in quality control during manufacture and for assessment of the stability samples of verapamil hydrochloride. To the best of our knowledge, a validated UPLC method which separates all the sixteen impurities disclosed in this investigation has not been published elsewhere. Total elution time was about 18min which allowed quantification of more than 100 samples per day. The analytical method discussed in British Pharmacopeia was pH sensitive and not compatible to LC-MS analysis but the method reported in this study is not involved any pH adjustment.