Forced Degradation Studies, Elucidation of Degradation Pathways and Degradation Kinetics of Xylopic Acid via LC and LC-MS/MS Analyses

Abstract

Stability studies of active pharmaceutical ingredients (APIs) remain an essential quality requirement of the pharmaceutical industry. Stability data of an API could guide in the choice of its processing technique, packaging method and storage conditions. Here, we sought to determine the stability or otherwise of xylopic acid (XA) under various stress conditions as stipulated by the International Conference on Harmonization (ICH). XA is a diterpene kaurene isolate of the African spice, Xylopia aethiopica (Annonaceae) that is credited with diverse biological activities. XA was subjected to various stress conditions (hydrolytic, oxidative, photolytic and thermal) and its degradation products characterized. Seven degradation products were identified and tentatively characterized by LC-MS/MS analysis. The probable degradation pathways for the seven degradation products were then predicted. Using a simple and validated UHPLC-DAD method, the degradation kinetics of XA under the different stress conditions were comprehensively assessed. The degradation of XA under all the stress conditions followed the first order reaction kinetics. XA was found to be less stable in strongly acidic or strongly basic solutions as well as in an oxidizing agent (hydrogen peroxide). The stability of XA was also found to be pH- and temperature-dependent. Its stability was however not affected by UV-light irradiation.

Keywords: Degradation products; Reaction kinetics; Stability; Stress conditions; Xylopic acid.