Next-generation capillary electrophoresis–mass spectrometry approaches in metabolomics

•CE–MS is an attractive analytical tool for analyzing the polar ionogenic metabolome.•A novel sheathless interface for CE–MS allows highly sensitive metabolic profiling.•Sheathless CE–MS enables in-depth metabolic profiling of volume-limited samples.•Multi-segment injection enables high-throughput CE–MS-based metabolomics studies.•Utility of CE–MS for clinical metabolomics requires study of large sample cohorts.

Capillary electrophoresis–mass spectrometry has shown considerable potential for profiling polar ionogenic compounds in metabolomics. Hyphenation of capillary electrophoresis to mass spectrometry is generally performed via a sheath–liquid interface. However, the electrophoretic effluent is significantly diluted in this configuration thereby limiting the utility of this method for highly sensitive metabolomics studies. Moreover, in this set-up the intrinsically low-flow property of capillary electrophoresis is not effectively utilized in combination with electrospray ionization. Here, advancements that significantly improved the performance of capillary electrophoresis–mass spectrometry are considered, with a special emphasis on the sheathless porous tip interface. Attention is also devoted to various technical aspects that still need to be addressed to make capillary electrophoresis–mass spectrometry a robust approach for probing the polar metabolome.

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