Degradation Pathways and Impurity Profiling of Pharmaceutical Drugs_ Macitentan Dasatinib Midostaurin Apalutamide Hydroxyzine Using Chromatography and Spectroscopy Techniques

Abstract

The impurity profiling study has significant advantages in the medicinal and pharmaceutical fields, where the purity, quality, and safety of the drug products are of utmost concern. Unquestionably, for a better and safer therapeutic use, liquid chromatography is being utilized to evaluate the impurities in pharmaceutical drugs. The degradation pathways and impurity profiling studies for anti-cancer drugs (Dasatinib tablets, Midostaurin soft-gel capsules, and Apalutamide tablets), anti- hypertensive drug (Macitentan tablets), and anti-histamine drug (Hydroxyzine hydrochloride tablets) were carried out and organized in six chapters for this thesis. In this research, new and reliable stability-indicating methods were developed utilizing high-performance liquid chromatography for the quantitative estimation of organic- related impurities (produced under drug stability and storage conditions) in pharmaceutical drug products. Using various stressing reagents, severe forced stress testing investigations were carried out, and the degradation routes for the chosen pharmaceutical products were evaluated. Unknown impurities produced under extreme forced stress testing were identified and characterized using spectrometric techniques like IR (FT-IR), LC-MS, LC-MS/MS and NMR (1H-NMR and 13C-NMR). The newly newlinedeveloped chromatographic methods of HPLC, LC-MS, and LC-MS/MS procedures were made it very easy and practical to quantify the organic-related impurities present in selected five pharmaceutical drugs, both in bulk drugs and in formulation. newline newline