Abstract

The efficient profiling of highly polar and charged metabolites in biological samples remains a huge analytical challenge in metabolomics. Over the last decade, new analytical techniques have been developed for the selective and sensitive analysis of polar ionogenic compounds in various matrices. Still, the analysis of such compounds, notably for acidic ionogenic metabolites, remains a challenging endeavor, even more when the available sample size becomes an issue for the total analytical workflow. In this paper, we give an overview of the possibilities of capillary electrophoresis‐mass spectrometry (CE–MS) for anionic metabolic profiling by focusing on main methodological developments. Attention is paid to the development of improved separation conditions and new interfacing designs in CE–MS for anionic metabolic profiling. A complete overview of all CE–MS‐based methods developed for this purpose is provided in table format (Table 1) which includes information on sample type, separation conditions, mass analyzer and limits of detection (LODs). Selected applications are discussed to show the utility of CE–MS for anionic metabolic profiling, especially for small‐volume biological samples. On the basis of the examination of the reported literature in this specific field, we conclude that there is still room for the design of a highly sensitive and reliable CE–MS method for anionic metabolic profiling. A rigorous validation and the availability of standard operating procedures would be highly favorable in order to make CE–MS an alternative, viable analytical technique for metabolomics.

Highlights

  • Metabolomics is considered within the field of analytical chemistry a well-accepted analytical approach for the global profiling of metabolites, i.e., small molecules with a molecular weight below 1500 Da

  • A rigorous validation and the availability of standard operating procedures would be highly favorable in order to make capillary electrophoresis-mass spectrometry (CE–MS) an alternative, viable analytical technique for metabolomics

  • The current work can be regarded as an important addition to our previous CE–MS-based metabolomics reviews [25,26,27,28,29,30], which we provide bi-annually for Electrophoresis and in which the usefulness and developments of CE–MS approaches for anionic metabolic profiling were not considered in detail so far

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Summary

Introduction

Authors found that the stability issue with the CE–MS method for anionic metabolic profiling appeared to be caused by corrosion of the stainless steel ESI needle when employing reversed CE polarity and negative ionization mode conditions. A platinum sprayer needle was used for CE–MS analysis in reversed polarity mode [24], the platinum sprayer is not necessary for anionic metabolic profiling when applying normal CE polarity at highpH separation conditions Because of these stability issues together with lower sensitivity using negative ionization mode detection, the perception had risen that CE–MS was not suitable for global metabolic profiling, especially when compared to other chromatographic techniques such as LC–MS and GC–MS.

Methodological developments
Improving reproducibility
Findings
Conclusions and perspectives
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