Capillary electrophoresis-mass spectrometry using a flow-through microvial interface for cationic metabolome analysis

The application of CE-MS in the field of metabolomics is underrepresented, even though it is in principle highly suited for the analysis of small charged compounds, as many metabolites are. Moreover, a robust coupling, using the sheath liquid (SL)-assisted interface was already presented more than a decade ago. A lack of concentration sensitivity is often mentioned as a reason for the underrepresentation of CE-MS in metabolomics. This is caused by postcolumn dilution of the sample with SL, which is typically delivered at a flow rate of 1-10 L/min. In this study, we investigated the performance of the flow-through microvial (MV) assisted CE-MS interface for cationic metabolomics. With this interface, only a little liquid is added postcolumn, that is, typically 100-500 nL/min. For the evaluation, we used a metabolite mix comprising 45 important cationic metabolites and compared the sensitivity and LOD of both devices. The performance of the CE-MS system was significantly improved by using the MV-assisted interface; the sensitivity was increased more than three times and the LOD decreased more than five times. Then, we analyzed single zebrafish embryos to demonstrate the method on a volume-limited biological sample. In comparison with SL-assisted CE-MS, twice as many molecular features were found, of which several could be identified. These results demonstrate the good potential of the MV interface for enhancing the coverage of the metabolome.