Validated Stability Indicating Chromatographic Methods for Determination of IvabradineHydrochloride in the Presence of Its Acidic Degradation Product

Two sensitive, accurate, precisestability indicating methods were developed and validated for the determination of IvabradineHCl (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 methodwas based on thin-layer chromatographic (TLC) separation of Iva from its degradation product, followed by densitometric measurement of the intact drug band at 286 nm. The separation was carried out on aluminium sheet of silica gel 60 F254 using methanol:chloroform:water (8:1:1 V/V) as the mobile phase, over a concentration range of 0.5–9 µg/band and mean percentage recovery of99.88 ± 0.994. The second method was based on reversed-phase high-performance liquid chromatography (HPLC), on C18 column using methanol:acetonitrile:phosphate buffer pH 3 (50:40:10 V/V) as the mobile phase at a flow rate of 1mL/min. Quantification was achieved with UV detection at 230 nm over a concentration range of 0.5–200 µg/mLwith mean percentage recovery of 99.98 ± 0.765.The developed methods were validated according to the ICH guidelines and were applied for bulk powder and dosage forms.