Response Surface Method Aided Development and Validation of Stability Indicating RP-HPLC-UV Method for Impurities of Dextromethorphan Hydrobromide in API and Three Marketed Formulations

Abstract

An innovative, specific, economical and precise method was developed and validated by employing reverse phase high performance liquid chromatography (HPLC) for contemporaneous estimation of dextromethorphan hydrobromide (DHB) along with its impurities in liquid formulation with forced degradation studies and confirmation of content of DHB in composition label in three market formulations along with their impurities were detected by this method. The optimized chromatographic conditions comprised of column (25 cm × 0.46 cm) × 5 μm Kromasil C8 bearing flow rate of 1.5 mL/min and wavelength 220 nm for UV-estimation. Design of experiments were implemented by following Box Behnken design with most optimum parameters selected as follows, column temperature (A), flow rate (B) and pH (C) with corresponding responses comprised of resolution between related compound A (RCA) and DHB (Y₁), tailing of DHB (Y₂) and resolution between related compound B (RCB) and DHB (Y₃). Stress testing was performed and proved that method was stable as no interfering peaks were observed. All validation parameters including suitability, linearity, accuracy, specificity, limit of detection, limit of quantitation, ruggedness, robustness and stress study were evaluated as per updated ICH guidelines and found to be within limit for pure DHB and detected impurities.