ICH GUIDANCE IN PRACTICE: DEVELOPMENT OF A VALIDATED STABILITY-INDICATING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC ASSAY METHOD FOR FEBUXOSTAT AND DEGRADATION KINETIC STUDY IN ACID HYDROLYTIC CONDITIONAbstract
The degradation behavior of Febuxostat was investigated under different stress degradation (hydrolytic, oxidative, photolytic and thermal) conditions recommended by International Conference on Harmonization (ICH) using HPLC and LCMS. Febuxostat was found to degrade signiﬁcantly in acidic and alkaline conditions as well as in neutral hydrolysis. The drug was stable to dry heat, photolytic degradation and under oxidative condition. Resolution of drug and the degradation products formed under different stress studies were successfully achieved on a C-18 column utilizing Methanol- water (with 0.02%v/v TFA) in the ratio of 95:5 and at the detection wavelength of 315 nm. The method was validated with respect to linearity, precision, accuracy, selectivity and speciﬁcity. The degradation kinetic of Febuxostat in acidic condition at different temperature was studied. The reaction order for Febuxostat in aqueous solvent system followed pseudo first order degradation kinetic. The catalytic rate constant and half-life at particular condition were determined. The Arrhenius plot showed the temperature dependence of Febuxostat.
Megha V. Sheth* and Jigar J. Pandya
Pharmaceutical Analysis and Quality Assurance Department, K.B. Raval College of Pharmacy, at Shertha, Post. Kasturinagar, Ta. & Dist. Gandhinagar-382423, Gujarat, India
05 November, 2012
06 December, 2012
25 January, 2013
01 February, 2013