Supercritical Fluid Chromatography-Mass Spectrometry, features and application for the analysis of pharmaceuticals, metabolites and lipids

In this PhD thesis,the hyphenation of supercritical fluid chromatography (SFC) with mass spectrometry (MS) has been studied regarding analytical performances and its application in metabolomics. The influence of a post-column liquid addition (make-up) and the effect of carbon dioxide have been studied regarding their impact on the ionization. The make-up allows the tuning of the ionization regardless of the chromatographic conditions and pushes the limits of quantification. SFC has also been hyphenated with high resolution MS doing data independent acquisition (DIA) SWATH/MS (sequential window acquisition of all theoretical mass spectra). Finally, online supercritical fluid extraction (SFE)-SFC-MS coupling has been investigated. Despite the obvious advantages of such a configuration, in particular the reduction of human manipulations during sample preparation, this configuration can be tricky particularly with regard to the applied extraction pressure which governs both the fluid density and the split ratio. This online extraction, analysis and detection system has been applied to the analysis of lipids in human plasma and shows potential for the analysis of complex matrices.