Stability indicating RP‐HPLC method for determination of dimethyl fumarate in presence of its main degradation products: Application to degradation kinetics

The first licensed polymerase inhibitor, baloxavir marboxil was recently approved for the treatment of influenza A and B viruses. Furthermore, there is growing interest in testing the antiviral activity of baloxavir marboxil against Coronavirus. Despite its critical clinical value, there is no information on the degradation products, pathways, or kinetics of baloxavir marboxil under various stress conditions. In this study, a new high‐performance liquid chromatography‐ultraviolet detection method for accurately quantifying baloxavir marboxil in the presence of its degradation products was developed. A study of degradation kinetics revealed that acidic, thermal neutral, and photolytic degradation reactions have zero‐order kinetics, whereas basic and oxidative degradation reactions have first‐order kinetics. The structural characterization of baloxavir marboxil degradation products was performed by coupling the optimized high‐performance liquid chromatography method to the triple‐quadrupole tandem mass spectrometer. The proposed approach was validated according to the International Council for Harmonisation Q2 (R1) requirements for accuracy, precision, robustness, specificity, and linearity. The validated new method was successfully used to analyze baloxavir marboxil as raw material and its pharmaceutical dosage form, Xofluza.

Section: Resultsmentioning

confidence: 99%

Kinetic degradation study for the first licensed anti‐influenza polymerase inhibitor, baloxavir marboxil, using high‐performance liquid chromatography‐mass spectrometry

Hafez

Abdel‐Halim

Hemdan

et al. 2022

“…Main effect plots (Figure S4) revealed that increasing SDS, Na 2 HPO 4 , and %butanol caused a decrease in run time but also efficiency (N) decreased and the tailing factor increased. Interaction plots (Figure S5) indicated that there were multiple interactions between studied factors and responses optimized, thus factorial design gave us more reliable conditions rather than one factor at a time optimization [41,42].…”

Section: Hplc Methods Development and Optimizationmentioning

confidence: 99%

Green micellar stability‐indicating high‐performance liquid chromatography method for determination of rupatadine fumarate in the presence of its main impurity desloratadine: Oxidative degradation kinetics study

Amer

Habib

Hammad

et al. 2023

Self Cite

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.

“…ICH guidelines [18] require developing stability indicating assay methods (SIAM) for active ingredients to elucidate drug inherent stability with time [19]; also, the linear regression analysis of degradation with time is required [20,21]. Degradation kinetics and pH profiling is required [22] for determining optimum storage conditions and predicting shelf life of drug [23,24].…”

Section: Introductionmentioning

confidence: 99%

Stability indicating RP‐HPLC method for methylcobalamin determination in different dosage forms: Application to photodegradation kinetics and pH rate profiling

Amer

Kamal

Hammad

et al. 2022

Self Cite

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.