Hydrolytic Degradation Profiling of Ezetimibe by HPLC Method

Background Forced degradation profiling is used to facilitate the development of analytical methodology, to gain a better understanding of active pharmaceutical ingredient (API) and drug product (DP) stability and it also part of new drug application (NDA) registration. Objectives To develop and validate a novel RP-HPLC method for determination of ezetimibe and forced degradation products and establish its intrinsic stability by forced degradation study. Methods Ezetimibe and its forced degradation products were successfully separated on Phenomenex, C18 column (250 × 4.6 mm, 5 μm) by mixture of methanol, water and acetonitrile (44:36:20) at 1 ml/min flow rate within 15 min and detection was performed by photodiode-array detector (PDA) at 248 nm. Results Ezetimibe was completely degraded into five degradants within 30 min in 50% methanolic 0.1 N NaOH at 60°C while it was degraded upto 71.3% into three degradants till 120 min in 50% methanolic 0.1N HCl at 600 C. Conclusions Drug was faster degraded in alkaline conditions than acidic conditions. The validated RP-HPLC method for ezetimibe may be applied for assay, stability-indicating assay, dissolution studies, as well as routine analysis in pharmaceutical industries.