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The development and biomedical uses of combined chromatographic - mass spectrometric techniques

Harrison, Mark Edward; (1991) The development and biomedical uses of combined chromatographic - mass spectrometric techniques. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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This thesis addresses the factors involved in the optimisation of the performance of a commercial thermospray source. This technique along with fast atom bombardment and electron impact ionisation were used in the application of mass spectrometry to quantitative measurements in toxicological and pharmaceutical studies. Many thermospray source designs incorporate a repeller electrode to enhance fragment production. It is known that any applied potential can affect the observed spectrum. Altering the position of this repeller was found to affect the influence its potential had on the quasimolecular ion species and on fragmentation. This was further investigated by using repellers of different shapes and designs. Acrylamide is a potent cumulative neurotoxin in animals and man. Acrylamide is a reactive electrophile which can form a covalent adduct with cysteine, and it has been shown that exposure can lead to a depletion in the levels of cellular glutathione. The kinetics of the reaction between glutathione and acrylamide was studied in solution by fast atom bombardment and thermospray mass spectrometry. To establish which was the most preferable technique for this purpose, the effects of pH, temperature and concentration on the rate of reaction were investigated. Direct monitoring of the reaction on the FAB probe was found to be unsuitable in this case. Thermospray was found to be more versatile for a wide range of reaction conditions. Chlormethiazole is a drug having sedative properties, which can be used in the treatment of drug withdrawal symptoms and insomnia. A gas chromatographic-mass spectrometric method was developed for assaying chlormethiazole in blood plasma at low concentrations, each step being investigated individually to validate and optimise the method. Clinical samples forming part of a study into the effect of chlormethiazole on spontaneous movement during the night in elderly patients were analysed.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The development and biomedical uses of combined chromatographic - mass spectrometric techniques
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Pure sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10106951
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