Gas‐phase ion–molecule reactions for the identification of the sulfone functionality in protonated analytes in a linear quadrupole ion trap mass spectrometer

Rationale The oxidation of sulfur atoms is an important biotransformation pathway for many sulfur‐containing drugs. In order to rapidly identify the sulfone functionality in drug metabolites, a tandem mass spectrometric method based on ion–molecule reactions was developed. Methods A phosphorus‐containing reagent, trimethyl phosphite (TMP), was allowed to react with protonated analytes with various functionalities in a linear quadrupole ion trap mass spectrometer. The reaction products and reaction efficiencies were measured. Results Only protonated sulfone model compounds were found to react with TMP to form a characteristic [TMP adduct–MeOH] product ion. All other protonated compounds investigated, with functionalities such as sulfoxide, N‐oxide, hydroxylamino, keto, carboxylic acid, and aliphatic and aromatic amino, only react with TMP via proton transfer and/or addition. The specificity of the reaction was further demonstrated by using a sulfoxide‐containing anti‐inflammatory drug, sulindac, as well as its metabolite sulindac sulfone. Conclusions A method based on functional group‐selective ion–molecule reactions in a linear quadrupole ion trap mass spectrometer has been demonstrated for the identification of the sulfone functionality in protonated analytes. A characteristic [TMP adduct–MeOH] product ion was only formed for the protonated sulfone analytes. The applicability of the TMP reagent in identifying sulfone functionalities in drug metabolites was also demonstrated. Copyright © 2016 John Wiley & Sons, Ltd.