title: Direct detection of a sulfonate ester genotoxic impurity by atmospheric-pressure thermal desorption-extractive electrospray-mass spectrometry.
abstract: A direct, ambient ionization method has been developed using atmospheric pressure thermal desorption-extractive electrospray-mass spectrometry (AP/TD-EESI-MS) for the detection of the genotoxic impurity (GTI) methyl p-toluenesulfonate (MTS) in a surrogate pharmaceutical matrix. A custom-made thermal desorption probe was used to the desorb and vaporize MTS from the solid state, by rapid heating to 200 °C then cooling to ambient temperature, with a cycle time of 6 min. The detection of MTS using EESI with a sodium acetate doped solvent to generate the [MTS+Na](+) adduct ion provided a significant sensitivity enhancement relative to the [M+H](+) ion generated using a 0.1% formic acid solvent modifier. The MTS detection limit is over an order of magnitude below the long-term daily threshold of toxicological concern (TTC) of 1.5 μg/g and the potential for quantitative analysis has been determined using starch as a surrogate active pharmaceutical ingredient (API).
authors.affiliation: Centre for Analytical Science, Department of Chemistry, Loughborough University, Leicestershire, LE11 3TU, United Kingdom.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Devenport
authors.forename: Laura C
authors.initials: LC
authors.lastname: Sealey
authors.forename: Faisal H
authors.initials: FH
authors.lastname: Alruways
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weston
authors.forename: James C
authors.initials: JC
authors.lastname: Reynolds
authors.forename: Colin S
authors.initials: CS
authors.lastname: Creaser
mesh_terms: D001274:Atmospheric Pressure; D009153:Mutagens / Q000032:analysis*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013814:Thermal Conductivity; D014105:Tosyl Compounds / Q000032:analysis*
chemical_list: D009153:Mutagens; D014105:Tosyl Compounds; C014108:methyl 4-toluene sulfonate