A mass spectrometry approach for identification and quantification of both polar and apolar metabolites from a single drop of human capillary blood

In the global effort of translating systems biology research into clinical applicability, metabolomics and lipidomics harbor great potential for blood-based medical diagnostics. Our lab has already established a robust analytical pipeline for the identification and quantification of polar metabolites by GC-MS. However, apolar metabolites, and lipids in particular, cover an important part of cell metabolism. Here we present a combined approach in order to detect (and quantify) both polar metabolites and lipid species from human blood using a two-step extraction procedure. Moreover, we developed a data analysis pipeline, which allows for the fast and robust quantification and identification of lipid species from high-resolution MS data. Isotope-corrected and calibrated mass traces are matched to an in-house database combining data from LipidMaps and HMDB. Internal standards serve as control for mass calibration as well as for abundance normalization for their respective lipid class. As proof of principle, we combined our approach to a simple, fast, and minimally invasive blood sampling method. Starting from 20 µL human capillary blood of 15 volunteers, about 100 known (+ 200 unidentified) polar metabolites and on average around 300 lipid species covering all main lipid classes were identified and quantified by GC-MS and direct infusion-MS, respectively.