Stability indicating HPLC Method Coupled with Fluorescence Detection for the Determination of Cyproheptadine Hydro-chloride in Its Tablets. Studies on Degradation Kinetics

Abstract

A sensitive, simple and rapid stability-indicating HPLC method using fluorescence detection was developed for the quantitative determination of the antihistaminic drug cyproheptadine hydrochloride (CYP). Good chromatographic separation was achieved using Shimadzu VP-ODS column (150 mm x 4.6 mm i.d., 5 μm particle size) and fluorescence detection at 410 nm after excitation 280 nm. Mobile phase consisting of methanol and 0.02 M phosphate buffer in the ratio of 65:35, v/v at pH 4.5 was pumped at a flow rate of 1 mL/min. Xipamide (XIP) was used as an internal standard (IS). The method was successfully applied to the analysis of CYP in its commercial tablets and the results were in good agreement with those obtained with the official USP method. The application of the proposed method was extended to stability studies of CYP after exposure to different ICH recommended stress conditions, such as acidic, alkaline, oxidative and photolytic degradation. Moreover, the method was utilized to investigate the kinetics of the oxidative degradation of CYP. The apparent first-order rate constant, half-life time, and activation energies of the degradation process were calculated. A proposal for the degradation pathway was presented.