Wilson, Derek J.2019-07-022019-07-022019-04-152019-07-02http://hdl.handle.net/10315/36339As the pharmaceutical industry moves towards larger protein-based therapeutics over chemically synthesized small molecules, there are increasing demands for parallel advancement in the technologies used for quality control of these biologically-derived products (biopharmaceuticals). This work describes the implementation of mass spectrometry (MS)-based methods in three areas where MS is well-positioned to fulfill unmet analytical needs. First, time-resolved electrospray ionization hydrogen-deuterium exchange (TRESI-HDX) and ion mobility spectroscopy (IMS)-MS were used to study conformational dynamics in transient Cytochrome c-lipid interactions. MS was also implemented for proteomic characterization of in-process and purified samples from acellular Pertussis vaccines. Further development of a targeted MS method is described for quantitation of two residual protein toxins, adenylase cyclase toxin (ACT) and dermoneucrotic toxin (DNT), and a glycopeptide, tracheal cytotoxin (TCT), from Bordetella pertussis. Collectively, the results highlight advancement in the application of structural and quantitative proteomics for more effective characterization of next generation biopharmaceuticals.enAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.Pharmaceutical sciencesElectronic Thesis or Dissertation2019-07-02BiochemistryChemistryMass spectrometryProtein dynamicsCytochrome cCardiolipinPhospholipidsMembraneProtein conformationTime-resolved electrospray ionizationTRESIHydrogen deuterium exchange mass spectrometryHDX-MSTime-resolved hydrogen deuterium exchangeTRESI-HDXHydrogen-deuterium exchangeHDXIon mobility spectrometryIMSBiopharmaceuticalsVaccinesBordetella pertussisPertussisWhooping coughQuantitationToxinsParallel reaction monitoringProtein quantitationProteomicsTargeted proteomicsAdenylase cyclase toxinDermoneucrotic toxinTrachael cytotoxinLiquid chromatographyLC-MSTandem mass spectrometryLC-MS/MSResidual toxins