유지선 (대웅제약 연구본부)

유지선 (대웅제약 연구본부)

박준석 (대웅제약 연구본부)

유지선 (대웅제약 연구본부)

김수민 (대웅제약 연구본부)

박준석 (대웅제약 연구본부)

Alkyl sulfonate ester compounds can be formed as by-products during the API manufacturing process, particularly under alkylation conditions or in the presence of fluorophenol derivatives as intermediates or starting materials. 3-Fluorophenyl methyl sulfonate (herein after FBS-OMe) and 3-fluorophenyl ethyl sulfonate (herein after FBS-OEt)​are such compounds, possessing alkyl sulfonate ester structures, and have been identified as genotoxic impurities (GTIs) based on positive results in the Ames test. Residual cases of alkyl sulfonate-type GTIs have been frequently reported in the literature and regulatory review documents, including those from the FDA. Given their high potential to remain in drug substances - especially active pharmaceutical ingredients (APIs) - quantitative control is required in accordance with ICH M7 guidelines.

In this study, we developed and validated a simultaneous analytical method for the quantification of 3-fluorophenyl methyl sulfonate and 3-fluorophenyl ethyl sulfonate using GC–MS/MS.