CE–MS for anionic metabolic profiling: An overview of methodological developments

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.

Enrichment-free analysis of anionic micropollutants in the sub-ppb range in drinking water by capillary electrophoresis-high resolution mass spectrometry

“…In the field of metabolomics, the use of CE-MS for nontargeted screening is already widely accepted and the strength of CE for the separation of highly polar and ionic substances as a complementary technique to RPLC was evaluated for many applications and matrices [22,30]. Even nanoflow interfacing techniques were already applied and non-targeted software solutions were developed to address the drawbacks of CE concerning migration time shifts by converting the time axis into effective mobility [31].…”

“…Furthermore, these interfaces produce smaller initial droplet sizes which is beneficial for gas-phase ion production and MS sampling. Enhancement of sensitivity by 30 to 100 times was reported in many applications such as protein analysis [21] and metabolomics [22] and also for small molecules like sulfonic acids [23], relevant for water analysis. However, to the best of our knowledge, there is no report on the direct screening (without SPE preconcentration) of ionic micropollutants in the submicrogram per liter range, as required for most cases when drinking water is analyzed.…”

The rise of the nanomaterial metabolite corona, and emergence of the complete corona

“…87 This technique is particularly suited for small highly polar metabolites and is capable of injecting from a very small sample volume (<5 μL) and is extensively reviewed for metabolomics analysis. [129][130][131] As with LC-MS, ionization is via ESI enabling metabolite database searches to be performed via the same (emerging) databases used for LC-MS based metabolomics.…”

Current applications of capillary electrophoresis‐mass spectrometry for the analysis of biologically important analytes in urine (2017 to mid‐2021): A review

“…The zones exiting the separation capillary are mixed with sheath liquid at a junction through a gap between the separation capillary and electrospray needle. More technical details about different ESI interface designs can be found in recent reviews [54][55][56][57].…”