Low level determination of p-toluenesulfonate and benzenesulfonate esters in drug substance by high performance liquid chromatography/mass spectrometry.

Abstract

GC/FID and HPLC/MS single ion monitoring methods have been evaluated for the determination of trace levels of methyl, ethyl and isopropyl esters of p-toluenesulfonic acid and methyl, ethyl, isopropyl and n-butyl esters of benzenesulfonic acid in drug substances. These sulfonate esters have been highlighted as potential genotoxins. HPLC/MS was found to be more promising and limits of quantification were between 2.5 and 5 ng/mL, which enabled detection limits in drug substance at 0.01-0.1 ppm for a 50 mg/mL solution. For one drug substance excellent recoveries of 94-95% were obtained at the 1.0 ppm level, however, with a second drug substance, a besylate salt, recoveries ranged from 86% to 100% and were dependant on the sample preparation. Limited stability of the sulfonate esters in various potential sample solutions indicated that samples may need to be prepared immediately before injection.