RESUMEN
A stability-indicating reverse phase-high-perfromance liquid chromatography method for the quantitative determination of dimethyl fumarate in presence of its main degradation products was developed. The chromatographic conditions were optimized using two-level full factorial design, chromatographic analysis was performed using Inertsil® column (250 × 4.6 mm, 5 µm) maintained at 25°C. Mobile phase was a mixture of water (pH 2.6 adjusted with phosphoric acid) and methanol (40:60, v/v) at a flow rate 1.0 mL/min, detection was performed at 210 nm using diode array detector. Stress degradation of dimethyl fumarate under acidic, alkaline, neutral, oxidative, photolytic, and thermal conditions was carried out, it was found to be very susceptible to hydrolysis under acidic and alkaline conditions; further investigation of degradation kinetics over pH range 1-9 was carried out. The degradation rate constant (K), t1/2 and t90 were calculated. Dimethyl fumarate show decreasing in stability in the following pH order: 7 < 5 < 3 < 1 < 9. The method was validated as per ICH guidelines, the method was found to be linear over concentration range 10-150 µg/mL with coefficient of determination (r2 ) 0.9997. The method was successfully applied for dimethyl fumarate determination in Marclerosis® dosage form within run time less than eight minutes without interference from excipients.
