Development and applications of an electrospray ionization ion trap/linear time-of-flight mass spectrometer

The work presented in this thesis involves the development and application of an electrospray ionization ion trap/time-of-flight mass spectrometer (ESI IT/TOFMS). The instrument combines the most universal ionization technique with the tandem mass spectrometry capability of an ion trap and rapid and sensitive detection provided by a time-of-flight detector.;Capabilities and limitations of this mass analyzer used for quantification of sulfonamides are presented. Compared to the performance of a single quadrupole mass spectrometer, the ESI IT/TOFMS is superior in analyses of multicomponent samples and applications requiring high rates of data acquisition. The instrument was also evaluated as a detector for identification of phenylthiohydantoin (PTH)-amino acids, the final products in the Edman sequencing of proteins. Detectability of PTH-amino acids in ESI IT/TOFMS is at least 10 times better than in commonly used liquid chromatography with UV-detection.;Implementation of tandem mass spectrometry (MS/MS) methods (e.g., source fragmentation, collision-induced dissociation (CID), and photo-induced dissociation (PID)) on the ESI IT/TOFMS is described. These techniques have been used to solve a number of challenging problems in structural analysis. Results from an in-depth investigation of the fragmentation pathways of PTH-amino acids have significance in understanding the fundamentals of ion chemistry and can be utilized for identification of nonstandard PTH-amino acids and differentiation of PTH-amino acid isomers.;A new method used to obtain unambiguous structural identification of polymer end groups is presented. This method, applied to the end-group analysis of two slow-releasing drugs, could become an essential part of a polymer characterization program.;The requirement for and limitation of MS/MS methods used in sequential analysis of biopolymers such as peptides, proteins, saccharides are evaluated and illustrated with examples. Time-resolved detection is used to characterize dissociation processes inside the ion trap in submillisecond time frame. This unique technique allowed for the first time to monitor time-resolved laser-induced dissociation of a protein inside the ion trap. The application of this method for dissociation kinetics of different conformers of cytochrome c and differentiation of disaccharide anomers is presented.