DEVENPORT, N.A. ... et al., 2013. Direct detection of a sulfonate ester genotoxic impurity by atmospheric-pressure thermal desorption−extractive electrospray−mass spectrometry. Analytical Chemistry, 85 (13), pp. 6224 - 6227.
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 longterm 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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This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and AstraZeneca [grant number BB/G017557/1].