Challenges in Analysis of Hydrophilic Metabolites Using Chromatography Coupled with Mass Spectrometry

Hydrophilic metabolites play important roles in cellular energy metabolism, signal transduction, immunity. However, there are challenges in both identification and quantification of the hydrophilic metabolites due to their weak interactions with C18-reversed-phase liquid chromatography (RPLC), leading to poor retention of hydrophilic metabolites on the columns. Many strategies have been put forward to increase the retention behavior of hydrophilic metabolites in the RPLC system. Non-derivatization methods are mainly focused on the development of new chromatographic techniques with different separation mechanisms, such as capillary electrophoresis, ion-pairing RPLC etc. Derivatization methods improve the hydrophobicity of metabolites and can enhance the MS response. This review mainly focused on the illustration of challenges of LCMS in the analysis of hydrophilic metabolomics field, and summarized the non-derivatization and derivatization strategies, with the intention of providing multiple choices for analysis of hydrophilic metabolites.