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Title: A study of capillary liquid chromatography-ion trap mass spectrometry for the analysis of drug metabolites : the effect of acridone derivatisation on peptide tandem mass spectrometry
Author: Hutton, K. A.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 2000
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This work discusses two applications of mass spectrometry in the pharmaceutical industry: capillary liquid chromatography/ion trap mass spectrometry of drugs and metabolites; and tandem mass spectrometry of derivatised peptides. A capillary liquid chromatography system was successfully coupled to an ion trap mass spectrometer using atmospheric pressure chemical ionisation. In order to do this a make-up liquid had to be added to provide sufficient flow for ionisation. A four-fold improvement in sensitivity was obtained over conventional liquid chromatography/mass spectrometry using atmospheric pressure chemical ionisation, despite the dilution effect of the make-up liquid. The capillary liquid chromatography system was also coupled to the ion trap using electrospray ionisation, which involved customisation of the source in order to maintain peak shape and maximise sensitivity. This system offered a forty-fold improvement in sensitivity over conventional liquid chromatography/electrospray mass spectrometry, reflecting the theoretical gain expected on changing to a capillary column. Product ion mass spectra of three drugs and their metabolites were obtained using both the ion trap and a triple quadrupole instrument. Both yielded good quality spectra, but the capability of the ion trap to perform sequential product ion scans meant that far more structural information could be obtained. The capillary liquid chromatography/ion trap mass spectrometry system thus offered advantages, in terms of both sensitivity and structure elucidation, over conventional liquid chromatography when coupled to a triple quadrupole mass spectrometer. The second section of this work examined the effect of acridone derivatisation of peptides prior to tandem mass spectrometric analysis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available