title: Gas-phase Smiles rearrangement in structural analysis of a pseudo-oxidative impurity generated in the pharmaceutical synthesis of S-(thiobenzoyl)thioglycolic acid.
abstract: Several mass spectrometry (MS) techniques including accurate MS and MS/MS, as well as hydrogen/deuterium (H/D) exchange, were utilized to characterize a pseudo-oxidative reaction by-product (impurity I) in the pharmaceutical synthesis of S-(thiobenzoyl)thioglycolic acid. The negative ion MS/MS data provided complementary structural information to the positive ion MS/MS data. An understanding of the gas-phase Smiles rearrangement upon collision-induced dissociation (CID) in the negative ion MS/MS mode played an important role in structural elucidation of impurity I. The theoretical calculations by density functional theory (DFT) at the B3LYP/6-311G(d,p) level provided insights into the thermochemistry of the Smiles rearrangement reaction. This pseudo-oxidative impurity is proposed to be generated via the base-catalyzed hydrolysis in solution.
authors.affiliation: Analytical Sciences, Chemical Development, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA. lianming.2.wu@gsk.com
authors.forename: Lianming
authors.initials: L
authors.lastname: Wu
authors.forename: Leon
authors.initials: L
authors.lastname: Zhou
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Vogt
authors.forename: David Q
authors.initials: DQ
authors.lastname: Liu
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D041961:Deuterium Exchange Measurement / Q000379:methods; D004340:Drug Contamination; D013058:Mass Spectrometry / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013864:Thioglycolates / Q000032:analysis* / Q000737:chemistry
chemical_list: D013864:Thioglycolates