The research presented in this dissertation involves the development of chiral and achiral analysis using capillary electrochromatography (CEC) and CEC coupled to mass spectrometry (CEC-MS). Chapter 1 briefly reviews CEC fundamentals and latest development on chiral CEC and CEC-MS. The CEC-UV enantioseparations for several acidic compounds are described in Chapter 2. The optimum resolutions for these acidic enantiomers are achieved in ion-suppression mode, i.e. with an acidic mobile phase. One of major drawback in coupling CEC with MS is the bubble formation at the column outlet end, resulting in irreproducible retention time and erratic baseline, or even current breakdown. By introducing internal tapered columns, the aforementioned limitations of CEC-MS are successfully overcome in Chapter 3. The CEC-MS enantioseparation of warfarin and coumachlor is carefully investigated and applied to quantify R- and S-warfarin in human plasma. For individual enantiomers, a concentration of 25 ng/mL is detectable. To further improve the robustness of CEC-MS column, a new procedure of fabricating internal tapered columns is reported in Chapter 4. These internal tapered columns demonstrate excellent ruggedness, low background noise, and good compatibility in reversed-phase and polar organic modes of CEC-MS. In chapter 5, the feasibility of using internal tapered columns packed with vancomycin chiral stationary phase (CSP) is explored for simultaneous enantioseparation of eight â-blockers using CEC-MS. After a careful optimization of the mobile phase composition, sheath liquid and spray chamber parameter, 15 out of 16 enantiomers could be simultaneously resolved with excellent efficiency and detection sensitivity. The synthesis and characterization of sulfated and sulfonated cellulose phenylcarbamate CSPs is described in Chapter 6. The use of these CSPs, especially the sulfonated one, significantly enhances the EOF profile and sample throughput but maintain high enantiomeric resolving power under various modes of CEC and CEC-MS. By combining CEC and atmospheric pressure photo-ionization (APPI) MS, Chapter 7 demonstrates the separation and detection of mono-methylated benzo[a]pyrene (MBAP) isomers with ~100 times enhancement on detection sensitivity than CEC-UV. In Appedix 2, monolithic columns are synthesized through photopolymerized sol-gel approach and utilized for CEC and CEC-APPI-MS of polyaromatic hydrocarbons, and alkyl phenyl ketones.

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An enantioselective heart-cut two-dimensional liquid chromatography-atmospheric pressure photoionization-tandem mass spectrometry method was developed for the analysis of 25 methylsulfonyl polychlorinated biphenyl metabolites in tissue extracts. Enantioseparation was achieved for 9 out of the 10 chiral analytes in less than 91 minutes, improving upon previous gas chromatography-based methods. Use of a pyrenyl-ethyl silica column in the first dimension enabled separation of all but two pairs of isobaric analytes. Limits of detection of 0.01 to 1.73 ng on-column were achieved. The precision and accuracy were within acceptable limits, but poor sensitivity was achieved for several meta-methylsulfonyl-substituted congeners. Despite this limitation, the method was successfully applied to the analysis of Greenland sledge dog (Canis familiaris) plasma and adipose tissue extracts. Concentration and enantiomer fraction data are presented. None of the target analytes were detected in Norwegian glaucous gull (Larus hyperboreus) plasma extracts.

Les leishmanioses sont des parasitoses en constante évolution, et l’accroissement d’apparitions de résistances vis-à-vis des traitements disponibles en fait une des préoccupations majeures des organismes de santé publique dans le monde. La miltefosine est actuellement le seul antileishmanien actif par voie orale. Son mécanisme d’action implique les lipides et notamment les phospholipides membranaires du parasite.Afin d’évaluer les effets de la miltefosine sur le parasite ainsi que les mécanismes de résistances, une étude lipidomique d’un clone de Leishmania donovani cultivé sous différentes conditions (traité, résistant, résistant-traité) a été réalisée dans le présent travail. Des analyses couplant une séparation des phospholipides en Chromatographie Liquide Haute-Performance à polarité de Phase Normale (NP-HPLC) avec un Spectromètre de Masse (MS) équippé d’une source d’Ionisation ElectroSpray (ESI) ont été traitées par chimiométrie, à l’aide d’une Correction Orthogonale du Signal suivie d’une Analyse Discriminante par Moindre Carrés Partiels (OSC-PLS-DA). Les principales espèces moléculaires permettant de distinguer les différentes cultures ont ensuite fait l’objet d’une identification structurale par spectrométrie de masse en tandem. Des hypothèses métaboliques ont pu être posées.Puis l’étude a été étendue à une plus grande variété de lipides, séparés par NP-HPLC. Pour cela une comparaison des sources d’ionisation à pression atmosphérique (ESI, Ionisation Chimique à Pression Atmosphérique et PhotoIonisation à Pression Atmosphérique) a été nécessaire afin de sélectionner la mieux adaptée pour un tel couplage. Les mécanismes d’action de la miltefosine et de l’amphotéricine B ont alors fait l’objet d’une étude lipidomique. / Leishmaniasis is a more and more spreading disease, and resistance of parasites toward antileishmanial drugs is a concern for public safety organizations troughout the world. Miltefosine is the only oral drug, and its mechanism of action implies membrane lipids, and phospholipids, of parasite cells.In order to assess this mechanism of action, and resistance mechanisms developed, a lipidomic study of Leishmania donovani strains (treated, resistant, treated-resistant) was performed in the present work. A Normal-Phase High-Performance Liquid Chromatography (NP-HPLC) was coupled to an ElectroSpray Ionisation Mass Spectrometer (ESI-MS) to analyze phospholipids, and data were computed using an Orthogonal Signal Correction-Partial Least Squares-Discriminant Analysis (OSC-PLS-DA). Molecular species responsible for the differenciation of strains were then structuraly identified using tandem mass spectrometry. Hypotheses on metabolic pathways implied were then proposed.The study was then extended to a broader range of lipids, also analyzed through NP-HPLC-MS. A comparison of Atmospheric Pressure Ion sources (ESI, Atmospheric Pressure Chemical Ionization and Atmospheric Pressure PhotoIonization) was thus necessary in order to select the most suitable source. A lipidomic study was then performed to assess mechanisms of action and mechanisms of resistance concerning miltefosine and Amphotericin B.

This study presents an analysis of the organic matter in meteorites, particularly carbonaceous chondrites (CCs), using advanced experimental techniques such as Two-step laser desorption laser ionization mass spectrometry (L2MS-oTOF) and Atmospheric Pressure Photoionization-Orbitrap (APPI-Orbitrap). The analysis focuses on the molecular complexity of both soluble (SOM) and insoluble (IOM) organic matter as well as the bulk rock and identifying and classifying different molecular families to understand the chemical composition of the meteorites. A new software tool, SpectraC, was developed to aid in analysing and comparing mass spectra from multiple meteorite samples simultaneously. The findings of the study reveal the complex chemical composition of meteorites, with condensed aromatics dominating most samples, and highlight the importance of using multiple techniques for a more complete understanding of the sample’s contents. This research lays the foundation for future work in astrochemistry, including the development of a state-of-the-art analytical tool and further exploration of the organic matter in meteorites. / Cette étude présente une analyse de la matière organique dans les météorites, en particulier les chondrites carbonées (CC), en utilisant des techniques expérimentales avancées telles que la spectrométrie de masse à ionisation laser par désorption en deux étapes (L2MS-oTOF) et l’ionisation photochimique à pression atmosphérique-Orbitrap  (APPI-Orbitrap). L’analyse se concentre sur la complexité moléculaire de la matière organique soluble (SOM) et insoluble (IOM) ainsi que sur la roche globale, et identifie et classe différentes familles moléculaires pour comprendre la composition chimique des météorites. Un nouvel outil logiciel, SpectraC, a été développé pour aider à analyser et comparer les spectres de masse de plusieurs échantillons de météorites simultanément. Les résultats de l’étude révèlent la composition chimique complexe des météorites, avec une domination des aromatiques condensés dans la plupart des échantillons, et mettent en évidence l’importance d’utiliser plusieurs techniques pour une compréhension plus complète du contenu des échantillons. Cette recherche pose les bases des travaux futurs en astrochimie, y compris le développement d’outils analytiques de pointe et l’exploration plus poussée de la matière organique dans les météorites.