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.
A stability‐indicating RP‐HPLC method for methylcobalamin determination was developed. Stress degradation under variable conditions was carried out. Methylcobalamin had pronounced susceptibility to hydrolysis under acidic, alkaline, and photolytic conditions; further study of photolytic degradation kinetics and pH rate profiling over pH range 2–11 was carried out. Photodegradation of methylcobalamin followed zero‐order kinetics with half‐life 0.99 h equivalent to 1971.53 lux. Methylcobalamin followed pseudo‐first‐order kinetics upon exposure to acidic and alkaline hydrolysis with highest stability at pH 5 and least stability at pH 2. Optimization of chromatographic conditions was performed using two level full factorial design, and chromatographic analysis was executed using Inertsil column (250 × 4.6 mm, 5 μm) maintained at 25◦C. Elution was carried out using 25 mM potassium dihydrogen phosphate (pH adjusted with phosphoric acid to 3.8): methanol:acetonitrile (55:35:10, v/v) as mobile phase. The flow rate was 1.0 ml/min. Detection was carried out at 220 nm using diode array detector. The method was validated as per ICH guidelines; the linearity was over concentration range 2–160 μg/ml with coefficient of determination 0.9995. The method was effectively applied for determination of methylcobalamin in Cobalvex ampoule, Cobal tablet, Cobal‐F tablet, and Methyltechon oral dissolvable film without interfering from excipients within run time 6 min.
A green micellar stability‐indicating high‐performance liquid chromatography method was developed for rupatadine fumarate determination in existence with its main impurity desloratadine. Separation was attained using Hypersil ODS column (150 × 4.6 mm, 5 μm), the micellar mobile phase consisted of 0.13 M sodium dodecyl sulfate, 0.1 M disodium hydrogen phosphate adjusted by phosphoric acid to pH 2.8 and 10% n‐butanol. The column was maintained at 45◦C and detection was carried out at 267 nm. A linear response was achieved over the range of 2–160 μg/ml for rupatadine and 0.4–8 μg/ml for desloratadine. The method was applied for rupatadine determination in alergoliber tablets and alergoliber syrup without the interference of methyl paraben and propyl paraben present as main excipients. Rupatadine fumarate revealed pronounced susceptibility to oxidation; further study of oxidative degradation kinetics was carried out. Rupatadine was found to follow pseudo‐first‐order kinetics when exposed to 10% H2O2 at 60 and 80°C and the activation energy was found to be 15.69 Kcal/mol. At a lower temperature (40°C), degradation kinetics regression was best fitted as a polynomial quadratic relationship, thus rupatadine oxidation at a lower temperature tends to adopt a second‐order kinetics rate. Oxidative degradation product structure was revealed using infrared and found to be rupatadine N‐oxide at all temperature values.
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