VALIDATED ANALYTICAL METHOD DEVELOPMENT AND CHARACTERIZATION OF FORCED DEGRADATIVE PRODUCTS OF MITAPIVAT AND THEIR TOXICITY PREDICTION BY IN-SILICO STUDIES

The current study reports to validate a stability indicating RP-HPLC method for estimation of mitapivat in bulk, pharmaceutical formulations and FD characterization by using MS method. The chromatographic separation was accomplished on Waters X-Bridge phenyl column (150× 4.6mm, 3.5µm). With the mobile phase consisting of acetonitrile and 0.1% OPA (80ː20v/v) at a flow rate of 1ml/min. The eluents were monitored by UV detector at 234nm. The developed liquid chromatographic method was validated with respect to accuracy, precision, linearity, robustness, range, limit of detection (LOD), limit of quantification (LOQ). The drug was subjected to various stress conditions such as acid, alkali, peroxide, reduction, photolytic, hydrolysis and thermal degradation. Among all the stress condition 5degradation products were obtained they were DP-1, Dp-2, Dp-3, Dp-4, Dp-5. They were subjected to mass characterization. The obtained structures were subjected to in-silico studies using Swiss ADME, pk CSM web server, protox2. The SWISS ADME web server and pk CSM web server were used for the prediction of pharmacokinetic properties and toxicity of the drug and its degradation products. The drug and the DP-1 don’t show any toxicity. Whereas DP-2, DP-3, DP-4, DP-5 shows immune toxicity. Hence the method was used for impurity profiling for mitapivat.