Approaches for improving throughput and sensitivity of LC-ESI-MS/MS analysis for small molecules in biological Samples

Diplôme Thèse Approaches for improving throughput and sensitivity of LC-ESI-MS/MS analysis for small molecules in biological Samples eng 2015-12-20 author Watanabe Kyoko 789389 director Hopfgartner Gerard 0000-0002-9087-606X 31827 10.13097/archive-ouverte/unige:82289 urn:nbn:ch:unige-822896 Sc. 4893 Liquid chromatography coupled to tandem mass spectrometry (LC-MS) has been used in the last two decades, in drug discovery or drug development as well as in therapeutic drug monitoring (TDM). Due to its high sensitivity and selectivity it is the method of choice for the quantification of drugs and metabolites in biological fluids. More and more the technique is also applied for multi-analytes quantification to support metabolomics studies. To improve sample throughput in TDM a dual Ultra High Performance Liquid Chromatography – Mass Spectrometry assay was developed and validated for the quantification of eight protease inhibitors in plasma and blood. Based on the same platform with two different chromatographic systems (pH 2.7 and pH 6.6) and the addition an automated on-line sample preparation step an assay method could be developed for the analysis of eighty-seven metabolites in plasma and blood. Finally the downsizing of the LC was investigated with the emphasis to improve the sensitivity of LC-MS assay when microsamples are available. Liquid chromatography Mass spectrometry Triple quadrupole mass spectrometer LC-MS LC-ESI-MS/MS Multiple reaction monitoring mode MRM HIV protease inhibitor Therapeutic drug monitoring TDM Dried blood spot DBS Metabolomics Dual UHPLC Column switching High throughput High sensitivity Micro LC-MS Endogenous metabolites Biological sample Dewey 615 31 Section des sciences pharmaceutiques 17 false 886 Spectrométrie de masse du vivant fe39a6a8-47cf-4f34-9647-307b4ec583ac Thesis Restricted Whole_thesis_Printing ver_160317.pdf 20687937 application/pdf Private 2018-03-23 58ad5cb8c2cd0154f28de3999b1ace628d0178834d28e8ccc74d7766f9acfdbb restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques

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Approaches for improving throughput and sensitivity of LC-ESI-MS/MS analysis for small molecules in biological Samples				2015	1,028	6

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Watanabe, Kyoko