Current state-of-the-art of nontargeted metabolomics based on liquid chromatography–mass spectrometry with special emphasis in clinical applications

•Current state-of-the-art on LC–MS based metabolomics is reviewed.•Recent advances to increase the metabolite coverage and improve the data quality are summarized.•Isotope coded derivatization methods and pseudo-targeted LC–MS methods are emphasized.•Data analysis methods and structural identification methods of metabolic ions are given.

Metabolomics, as a part of systems biology, has been widely applied in different fields of life science by studying the endogenous metabolites. The development and applications of liquid chromatography (LC) coupled with high resolution mass spectrometry (MS) greatly improve the achievable data quality in non-targeted metabolic profiling. However, there are still some emerging challenges to be covered in LC–MS based metabolomics. Here, recent approaches about sample collection and preparation, instrumental analysis, and data handling of LC–MS based metabolomics are summarized, especially in the analysis of clinical samples. Emphasis is put on the improvement of analytical techniques including the combination of different LC columns, isotope coded derivatization methods, pseudo-targeted LC–MS method, new data analysis algorithms and structural identification of important metabolites.