<b>Application of Tandem Mass Spectrometric Methods Based on Gas-phase Ion-molecule Reactions for the Characterization of Borate Radical Anions and Identification of Functional Groups in Drug Metabolites</b>

<p dir="ltr">Mass spectrometry (MS) is a versatile and powerful analytical tool that is extensively used for determining the elemental composition and structures of unknown compounds. Multiple-stage tandem mass spectrometry (MSⁿ) based on collision-activated dissociation (CAD) and/or ion-molecule reactions can be used to characterize charged reaction intermediates and to identify specific functional groups in unknown ionized analytes. The research described in this dissertation focuses on the development of tandem mass spectrometric methods based on gas-phase ion-molecule reactions and CAD for the chemical characterization of the unusual binding properties of several electrophilic <i>closo</i>-borate radical anions. These anions are known to stabilize highly reactive cations in chemical synthesis and catalysis and therefore have various applications in medicine. Moreover, this serves as an important preliminary step toward applying these ions in preparative mass spectrometry experiments, for example, enabling the controlled synthesis of new compounds in surface layers by using reactive gas-phase ions. Furthermore, this dissertation discusses the development of a tandem mass spectrometric method based on diagnostic gas-phase ion-molecule reactions for the identification of aromatic aldehyde and keto functionalities in protonated analytes. These functionalities are present in some potentially mutagenic drug impurities and therefore, their identification is of utmost importance to the pharmaceutical sector. Finally, the application of MS³ experiments combining gas-phase ion-molecule reactions followed by CAD on specific product ions are discussed to facilitate the differentiation of nucleophilic compounds whose nucleophilic atom is bound to at least one H atom or has a nearby labile H atom from compounds that do not. The development of such analytical techniques enables the reliable characterization of both previously known (targeted analysis) and unknown drug impurities (nontargeted analysis) during and after the drug development process.</p>