Comprehensive Analysis of Deflazacort Oxidative Degradation: Insights into Novel Degradation Products and Mechanisms.

Abstract

The oxidative degradation pathways of deflazacort (DFL) were investigated to address the gap in understanding its degradation products, focusing on reactions with oxidative stressors such as hydrogen peroxide and 4,4'-azobis (4-cyanovaleric acid) (ACVA). Using HPLC-PDA, high-resolution mass spectrometry (HRMS), NMR and IR spectroscopy, four novel degradation products were identified and structurally characterized. Two of these products were isolated using preparative HPLC before characterization. Hydrogen peroxide led to the formation of three novel products (DP-1, DP-2, and DP-3), while ACVA resulted in a single novel product (DP-4). Mechanistic and kinetic experiments supported the proposed degradation pathways under the various oxidative stress conditions studied, revealing distinct rates of formation for the degradation products during the time-course study. The identification and detailed structural elucidation of these degradation products provide critical insights into the chemical stability and potential reactivity of DFL under oxidative stress. These findings underscore the importance of comprehensive stability testing for ensuring drug safety and efficacy, and offer valuable data for future research on the toxicity and pharmacological impact of DFL degradation products.