Direct Detection of a Sulfonate Ester Genotoxic Impurity by Atmospheric-Pressure Thermal Desorption–Extractive Electrospray–Mass Spectrometry

Neil A. Devenport, Laura C. Sealey, Faisal H. Alruways, Daniel J. Weston, James C. Reynolds, and Colin S. Creaser

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).

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A new strategy based on real-time secondary electrospray ionization and high-resolution mass spectrometry to discriminate endogenous and exogenous compounds in exhaled breath

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Human Breath Analysis May Support the Existence of Individual Metabolic Phenotypes