Identification and Structure Elucidation of Novel Forced Degradation
Products of Gimeracil
Abstract
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.