Sulconazole has been reported to degrade into sulconazole sulfoxide via sulfur oxidation; however, structural characterization data was lacking and the potential formation of an N -oxide or sulfone could not be excluded. To clarify the degradation pathways and incorporate the impurity profile of sulconazole into the United States Pharmacopeia–National Formulary ( USP–NF ) monographs, a multifaceted approach was utilized to confirm the identity of the degradant. The approach combines stress testing of sulconazole nitrate, chemical synthesis of the degradant via a hydrogen peroxide-mediated oxidation reaction, semi-preparative HPLC purification, and structural elucidation by LC–MS/MS and NMR spectroscopy. Structural determination was primarily based on the comparison of spectroscopic data of sulconazole and the oxidative degradant. The mass spectrometric data have revealed a McLafferty-type rearrangement as the characteristic fragmentation pathway for alkyl sulfoxides with a β -hydrogen atom, and was used to distinguish the sulfoxide from N -oxide or sulfone derivatives. Moreover, the generated sulconazole sulfoxide was utilized as reference material for compendial procedure development and validation, which provides support for USP monograph modernization.
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