Methane Elimination upon Collision-Activated Dissociation of Selected Product Ions Formed Upon Gas-Phase Reactions of (Isopropenyloxy)trimethylsilane Facilitates the Mass Spectrometric Classification of Specific Oxygen- and/or Nitrogen-Containing Compounds.

Unambiguous identification of drug impurities is of the utmost importance for the pharmaceutical sector. Therefore, access to analytical techniques that enable the reliable characterization of drug impurities during and after the drug development process is required. In this study, tandem mass spectrometry combined with gas-phase ion-molecule reactions followed by collision-activated dissociation (CAD) of specific ion-molecule reaction product ions is demonstrated to enable the identification of nucleophilic compounds with at least one H atom on their nucleophilic atom or a H atom on an adjacent heavy atom. Compounds with different oxygen- and/or nitrogen-containing functionalities and their combinations, such as carboxylic acids, phenols, aldehydes, hydroxylamines, amides, anilines, and sulfonamides, were tested. All analytes were protonated via atmospheric pressure chemical ionization (APCI), transferred into a linear quadrupole ion trap, isolated, and allowed to react with (isopropenyloxy)trimethylsilane (ITS). All protonated compounds studied, including the ones mentioned above as well as many others, react with ITS to form an addition product that has eliminated an acetone molecule. Subjecting these product ions to CAD generated diagnostic fragment ions via the loss of methane for most of the compounds with at least one H atom on their nucleophilic atom or a H atom on an adjacent heavy atom. Only three exceptions were identified. Quantum chemical calculations were employed to delineate the likely mechanisms for the formation of the relevant product ions upon ion-molecule reactions and their fragmentation via elimination of methane.