Identification and Characterization of Acidic Degradation Products of Moxidectin Drug Substance Including Degradation Pathways Using LC, HRMS, and NMR.

This article focuses on the development and validation of an improved stability-indicating high-performance liquid chromatography (HPLC) method for analyzing moxidectin, a broad-spectrum antiparasitic active pharmaceutical ingredient (API) used in human and veterinary medicine. The study identifies that under acidic conditions, the previously reported degradation product 3,4-epoxy-moxidectin was not detected; instead, the impurity at relative retention time (RRT) 1.2 was characterized as (23Z)-moxidectin, an oxime geometric isomer of moxidectin, through high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) analyses. The research elucidates the acid-catalyzed degradation pathway involving imine isomerization and hydrolysis, highlighting the influence of acid strength and nucleophilic salts on the process. The newly developed HPLC method, employing a superficially porous particle column and optimized temperature and flow conditions, achieves effective separation of critical impurities, including (23Z)-moxidectin and 3,4-epoxy-moxidectin, thereby enhancing quality control and stability assessment of moxidectin drug substances in compliance with regulatory standards.