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Title: A study of liquid chromatography-particle beam mass spectrometry and its application to problems in drug metabolism and bioanalysis
Author: Harris, A. J.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 1999
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Liquid chromatography-particle beam mass spectrometry was invented to provide a method for acquisition of library-searchable electron impact and chemical ionisation data for compounds in complex mixtures. My studies explore the potential of using this technique for quantitative and qualitative applications in the areas of drug metabolism and bioanalysis. A systematic evaluation of the key operational variables is conducted, providing a basis for the development of a novel optimisation procedure which takes account of the interactive nature of many of these variables. The origin of carrier effects is discussed. The various hypotheses suggested previously by other workers to account for carrier effect are considered but I conclude that none of these, alone or in combination, can explain all of the accumulated experimental evidence. This infers the involvement of at last one other factor: I believe this to be variability in particle morphology. The evidence to support this proposal is described. The spectral data obtained by particle beam mass spectrometry can be extremely useful for structural studies. Examples are discussed where it proved superior to tandem mass spectrometry but generally, the two approaches are complementary. This is exemplified by a case where both techniques were necessary to elucidate some highly unusual biotransformations of an antiviral compound. For quantitative applications, atmospheric pressure ionisation has made other interfaces largely redundant, but examples are given where the alternative ionisation mechanisms available with particle beam yielded superior results. The complementary nature of these techniques is illustrated by descriptions of analyses by particle beam for a non-polar compound, and an electrospray assay method for a polar compound. The thesis concludes with a brief discussion of the future of particle beam mass spectrometry in the drug metabolism environment, and warns that unless improvements to interfaces are made, there is a danger that what is potentially a very useful technique may disappear.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available