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Title: The automation and validation of LC/MS/MS and its application to pharmacokinetic and drug metabolism studies
Author: Lively, J. D.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 2000
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The studies described in this thesis have investigated the complexities of automating Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS) systems, both in terms of sample introduction and data processing, and their subsequent testing and validation. Atmospheric pressure ionisation sources have revolutionised the use of mass spectrometry in the last 10 years. With the use of these robust and universal sources, large numbers of samples can now be processed in a single bioanalytical run. This has driven the need for high sample throughput automation. Described within are applications exploiting the versatility of the Gilson Automated Sample Processor using Extraction Columns (ASPEC) XLi Cartesian robot. In order to process the ever-increasing sample data, and to relieve this bottleneck in bioanalysis, in-house Interactive Chemical Information Software (ICIS-IIITM) scripts were written and developed. The validation of the Finnigan MAT TSQ 700 mass spectrometer and its ancillaries, including the in-house written software, to Good Laboratory Practice (GLP) standards are described in detail. In addition, and as a further demonstration of the robustness and versatility of LC/MC/MC, the analysis of a compound extracted from dog lung homogenate following a novel solid phase extraction (SPE) method is recapitulated. A strategy for the method development of LC/MS/MS bioanalytical assays is likewise included.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available