Identification and Structure Elucidation of Novel Forced Degradation Products of Gimeracil

Rationale: The study aims to explore the degradation products of gimeracil via forced degradation analysis, necessitating the development of an analytical method for liquid chromatography-mass spectrometry (LC-MS). Methods: Gimeracil was subjected to various stress conditions in accordance with International Conference on Harmonization guidelines, including acidic, alkaline, oxidative, photolytic, and thermal conditions. The analytical method was optimized to effectively separate gimeracil from its potential degradation products. Results: Under acidic, alkaline, photolytic, and thermal conditions, minimal degradation of gimeracil was observed. However, oxidative stress led to significant degradation, resulting in the identification of fourteen previously unreported degradation products. Structural elucidation of these products was achieved through orbitrap HRMS (high-resolution mass spectrometry) and HRMS/MS spectra analysis, with pathways for the formation of various daughter ions provided for some degradation products. Conclusion: Forced degradation analysis revealed the susceptibility of gimeracil to oxidative stress, leading to the generation of numerous degradation products. The developed LC-MS method proved effective in separating gimeracil from its degradation products, enabling comprehensive structural elucidation and identification.