Stability Indicating Spectrophotometric Methods for Determination of Ivabradine Hydrochloride in the Presence of Its Degradation Product

Abstract

Five simple, specific, accurate and precise stability indicating spectrophotometric methods have been developed for determination of Ivabradine HCl (Iva) in the presence of its acid degradate, in bulk powder and in pharmaceutical formulations. Forced degradation was performed using 2N HCl. The degradation product was identified by infrared spectroscopy and mass spectrometry, and the pathway of degradation was illustrated. The first method is a second derivative (D2) spectrophotometric method, which allows the determination of Iva in presence of its degradate at 290 nm. The second method is the first derivative of the ratio spectra (1DD) by measuring the peak amplitude at 294 nm. The third method is the ratio difference (RD) method which depends on measuring the difference between the amplitudes of the ratio spectra at 249 nm and 298 nm. The fourth method is the constant center (CC) method where the original spectra of Iva were obtained. The fifth method is mean centering of ratio spectra (MCR). The proposed methods were validated according to ICH guidelines. The obtained results were statistically compared with those of a reported HPLC method. The comparison showed that there is no significant difference between the proposed methods and the reported method regarding both accuracy and precision.