D. Singh, A. Sahu, A. Wani
Mar 12, 2020
Citations
1
Influential Citations
7
Citations
Journal
Journal of pharmaceutical sciences
Abstract
Bepotastine (BPT) is a H1-receptor antagonist. It is used as a besilate salt in ophthalmic solution for allergic conjunctivitis, and orally for the treatment of allergic rhinitis and utricaria/pruritus. Its systematic forced degradation study is unreported. The same was carried out in different conditions prescribed by International Conference on Harmonisation. The stressed solutions were subjected to reversed phase liquid chromatographic analysis, and BPT was observed to be labile under photobasic condition only, yielding five photodegradation products. The structures of the latter were elucidated from data generated using liquid chromatography-high resolution mass spectrometry and multi-stage mass spectrometry. Of the five, four products were further isolated and subjected to nuclear magnetic resonance spectroscopy to justify the proposed structures. Two of them, with similar accurate mass, were additionally and unambiguously characterized from their heteronuclear multiple bond correlation data, hydrogen deuterium exchange mass data, and quantum chemical analysis using density function theory calculations. One degradation product had a structure that could only be explained by unusual rearrangement involving conversions of N-oxide into hydroxylamine, similar to Meisenheimer rearrangement. The physicochemical, as well as absorption, distribution, metabolism, excretion and toxicity properties of BPT and its characterized photodegradation products were evaluated in silico by ADMET Predictor™ software.