Persistent Link:
http://hdl.handle.net/10150/185490
Title:
Biomedical applications of mass spectrometry.
Author:
McClure, Thomas Dale.
Issue Date:
1991
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The application of mass spectrometry to verification of the structure of 3-methyluridine (m³U) isolated by HPLC from normal human urine is described. m³U has been used as an internal standard for studies of urinary nucleosides, a practice that is discouraged with the confirmation of m³U as a naturally occurring compound. Mass spectrometry has been used for the identification of 5'-deoxyxanthosine (5'-dX) a novel nucleoside in normal human urine. Initial concern over availability of a reference sample of 5'-dX prompted investigations of the structure/fragmentation relationships of the TMS deratives of 2'-, 3'-, and 5'-deoxynucleosides toward differentiation between the three deoxynucleosides. Results are presented which allow discrimination between the model compounds, deoxyanalogs of adenosine. Subsequent to the deoxynucleoside fragmentation studies, a biosynthetically produced reference sample of 5'-dX became available for direct comparison of mass spectra and chromatographic retention times which, when combined with observations from the deoxynucleoside studies established the structure of 5'-dX. In response to the large number of mass spectra produced from the GC-MS analysis of a TMS derivatized urine sample, computer software has been written to aid in spectral analysis. Examples are shown in which the software uses established fragmentation rules to assign structure to ions in the mass spectrum and suggest modifications in the sugar portion of two urinary nucleosides. The structure/fragmentation relationships of the unique antitumor drug taxol has been studied by EI, CI and FAB mass spectrometry. Information is presented showing characteristic fragmentation of the side-chain and verification of functional groups attached to the taxane ring. Studies have been conducted to determine the relationship between target temperature and matrix and sample lifetime in the source of the mass spectrometer. Results are presented showing that cooling the target permits the use of matrix materials that are too volatile at ambient temperatures thus extending the range of compounds that can be studied by mass spectrometry. A recently constructed four-sector mass spectrometer is described with a detailed discussion of instrumental capabilities. Results of experiments designed to apply these capabilities to the structural analysis of TMS nucleosides using FAB ionization are discussed with an emphasis on the fragmentation unique to 4-sector daughter ion experiments compared with conventional studies and 2-sector daughter ion results.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Dissertations, Academic; Chemistry, Analytic; Mass spectrometry.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmaceutical Sciences; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Schram, Karl H.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleBiomedical applications of mass spectrometry.en_US
dc.creatorMcClure, Thomas Dale.en_US
dc.contributor.authorMcClure, Thomas Dale.en_US
dc.date.issued1991en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe application of mass spectrometry to verification of the structure of 3-methyluridine (m³U) isolated by HPLC from normal human urine is described. m³U has been used as an internal standard for studies of urinary nucleosides, a practice that is discouraged with the confirmation of m³U as a naturally occurring compound. Mass spectrometry has been used for the identification of 5'-deoxyxanthosine (5'-dX) a novel nucleoside in normal human urine. Initial concern over availability of a reference sample of 5'-dX prompted investigations of the structure/fragmentation relationships of the TMS deratives of 2'-, 3'-, and 5'-deoxynucleosides toward differentiation between the three deoxynucleosides. Results are presented which allow discrimination between the model compounds, deoxyanalogs of adenosine. Subsequent to the deoxynucleoside fragmentation studies, a biosynthetically produced reference sample of 5'-dX became available for direct comparison of mass spectra and chromatographic retention times which, when combined with observations from the deoxynucleoside studies established the structure of 5'-dX. In response to the large number of mass spectra produced from the GC-MS analysis of a TMS derivatized urine sample, computer software has been written to aid in spectral analysis. Examples are shown in which the software uses established fragmentation rules to assign structure to ions in the mass spectrum and suggest modifications in the sugar portion of two urinary nucleosides. The structure/fragmentation relationships of the unique antitumor drug taxol has been studied by EI, CI and FAB mass spectrometry. Information is presented showing characteristic fragmentation of the side-chain and verification of functional groups attached to the taxane ring. Studies have been conducted to determine the relationship between target temperature and matrix and sample lifetime in the source of the mass spectrometer. Results are presented showing that cooling the target permits the use of matrix materials that are too volatile at ambient temperatures thus extending the range of compounds that can be studied by mass spectrometry. A recently constructed four-sector mass spectrometer is described with a detailed discussion of instrumental capabilities. Results of experiments designed to apply these capabilities to the structural analysis of TMS nucleosides using FAB ionization are discussed with an emphasis on the fragmentation unique to 4-sector daughter ion experiments compared with conventional studies and 2-sector daughter ion results.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectDissertations, Academicen_US
dc.subjectChemistry, Analyticen_US
dc.subjectMass spectrometry.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmaceutical Sciencesen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorSchram, Karl H.en_US
dc.contributor.committeememberRemers, William A.-
dc.contributor.committeememberMartin, Arnold-
dc.contributor.committeememberDenton, M.B.-
dc.identifier.proquest9127707en_US
dc.identifier.oclc710834680en_US
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