title: 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.
authors.affiliation: AstraZeneca, Process R&D, Department of Analytical Chemistry, Loughborough, Leicestershire, UK. graham.taylor@astrazeneca.com
authors.forename: Graham E
authors.initials: GE
authors.lastname: Taylor
authors.forename: Mark
authors.initials: M
authors.lastname: Gosling
authors.forename: Andrea
authors.initials: A
authors.lastname: Pearce
mesh_terms: D001557:Benzenesulfonates / Q000032:analysis*; D002264:Carboxylic Acids / Q000032:analysis; D002747:Chlorpropamide / Q000031:analogs & derivatives / Q000032:analysis; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D004952:Esters / Q000032:analysis*; D013058:Mass Spectrometry / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D000096926:Benzenesulfonamides
chemical_list: D001557:Benzenesulfonates; D002264:Carboxylic Acids; D002747:Chlorpropamide; D004952:Esters; D004364:Pharmaceutical Preparations; C111224:API 2; D000096926:Benzenesulfonamides; C029501:4-toluenesulfonic acid