Development and Validation of Stability-Indicating HPLC Method for Estimation of Sertaconazole Nitrate in Bulk and Topical Formulation: Application to Chemical Kinetics, Characterization and in silico Toxicity Prediction of its Acid Degradation Product

Abstract

A simple, accurate, precise and specific stability-indicating HPLC method was developed and validated for estimation of sertaconazole nitrate (SRT) in bulk and topical formulation. The drug and cream containing SRT were subjected to forced degradation conditions and the formed degradation products were well separated and resolved from the drug and excipients on C18 column (250 × 4.6 mm, 5 μm) using blend of acetonitrile: methanol: 30 mM potassium phosphate buffer (pH 3.0) (60: 20: 20 %, v/v) in isocratic mode at a flow rate of 1.2 mL/min. All eluents were detected using multi-channel wavelength detector at 260 nm. The drug was found to degrade under acid, alkali, wet heat and to oxidative conditions but found stable under dry heat and photolytic conditions. The method was validated as per ICH guidelines. The chemical kinetic studies for acid and alkali hydrolysis shows that the SRT follows the pseudo-first order reaction rate and have more rate of reaction for acid hydrolysis than alkali hydrolysis. The acid degradation product was synthesized and characterized using, NMR and mass spectrum as 1-(2,4-dichlorophenyl)-2-2(1H-imidazole-1-yl) ethanol and its toxicity profile was studied using TOPKAT.