Development of Tandem Mass Spectrometric Methods and Instrumentation for the Structural Elucidation of Unknown Drug Metabolites Based on Ion/Molecule Reactions

Mass spectrometry has proven to be an invaluable tool for the analysis of compounds in complex mixtures. High resolution mass spectrometry provides elemental compositions of compounds. Tandem mass spectrometry (MSn) utilizing collision-activated dissociation (CAD) or ion/molecule reactions has become a powerful technique for structural elucidation of unknown compounds. Further, the coupling of MSn with a separation technique, such as high performance liquid chromatography (HPLC), enables the analysis of trace level analytes in complex mixtures. This dissertation focuses on the development of MSn methodologies and instrumentation for the structural elucidation of unknown compounds. While CAD is the most common MSn technique used for the characterization of ionized compounds, it does not always allow for the differentiation of isomeric molecules. Gas-phase ion/molecule reactions provide an alternate route to probe the structures of ionized or neutral compounds. This approach combined with linear quadrupole ion trap (LQIT) mass spectrometry was used to develop methods for the identification of different functional groups in polyfunctional analytes and for the differentiation of isomers. Finally, a device was built that enables the examination of ion/molecule reactions in an automatic high-throughput manner