Using Ultrahigh-Resolution Mass Spectrometry to Unravel the Chemical Space of Complex Natural Product Mixtures

Complex environmental and biological samples contain an enormous pool of abiotic and biotic low-molecular-weight natural products. The analysis of the entity of metabolites, in general referred to as metabolomics, is an important step toward the discovery of novel molecular structures in any type of organism as well as to improve the understanding of cellular regulation and adaption processes. Natural product analysis by means of metabolomics benefits from recent improvements in sampling and separation technologies such as solid-phase extraction (SPE), ultraperformance liquid chromatography (UPLC), and multidimensional chromatography, as well as from improved resolution and sensitivity in organic structural spectroscopy, namely infrared (IR) and Raman spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and especially mass spectrometry. A combination of pathway mapping, statistical analysis, and mass defect filtering can be applied to focus on most important compounds or series of structurally related natural products.