Lipids are ubiquitous biomolecules essential to all life, found in every cellular type, ranging from the human body and vegetal organisms, down to bacteria. They have various structures and many different functions in cell structuration, energy storage or signalling. Lipids are the main constituent of skin, and are constituted mainly by ceramides with prevalent very long acyl chains, free fatty acids, and cholesterol. They are required for the maintenance and regulation of the epidermal barrier, physical properties of the skin, and defence against microbes. In skin aging context the full characterization of the skin lipidome is essential especially the analysis of skin ceramide which is a large and complex family of 12 sub-classes. There are relatively few methods available to study them and their analysis remains challenging. In this presentation, we will present an original profiling of these metabolites using supercritic fluid chromatography (SFC) coupled to high resolution mass spectrometry (MS) which is especially suitable for this apolar metabolites. First we will present the optimization of skin extraction, then the development of the analytical method on SFC-QTOF Xevo (Waters) with the chromatographic separation on different column via combination of solvents and gradient and finally the MS detection through source temperature and the make-up optimization. Due to the very few standards available, the MS/MS characterization of each subclasses will be also presented. And finally a home-made data base, containing m/z a retention time for each species, was constituted with 230 species. The SFC-HRMS data set obtained in such a large lipidomic profiling required a complex data treatment and unfortunately software solutions of suppliers are rarely adapted to our needs, here MS-DIAL was used to reprocess these data in a semi targeted mode. And to conclude some example of complete lipidomic profiling of skin sample will be presented.