1. Investigación

Metabolites are the final products of the metabolism and are, therefore, directly related to phenotype. They constitute the metabolome of an organism. The wide diversity of the physicochemical properties of the metabolites in terms of molecular weight, concentration, polarity, volatility, solubility, pKa, and charge makes their analysis a remarkable challenge. With over 220,000 metabolites recorded in the HMDB database, there is no single analytical technique capable of analyzing all of them. Therefore, multiple analytical platforms are required to obtain a comprehensive picture of the metabolome. Among these platforms, mass spectrometry (MS)-based analytical techniques are among the most widely used. Capillary electrophoresis (CE) coupled to MS has been employed to analyze polar/ionic metabolites. Although this technique is not widely used, it has demonstrated unique capabilities for the detection of polar and ionic metabolites that are an essential part of the metabolome and are not usually detected by other techniques. This review highlights the role of CE-MS in untargeted metabolomics, particularly in comparison to the hydrophilic interaction chromatography (HILIC) separation mode. Additionally, we discuss the metabolomics workflow in CE-MS for untargeted metabolomics, including sample treatment and analysis, data treatment, and metabolite annotation. We notably present the annotation tools developed explicitly for CE-MS, as well as some computational alternatives, in-house libraries of relative migration times, effective mobility, MS/MS fragmentation, in-source fragmentation, and the CEU Mass Mediator online tool. Finally, we mention future perspectives of this technique, such as single cell-CE and ion mobility (IM)-MS. Overall, this review shows the important role of CE-MS in the studies of untargeted analysis published in the last five years to approach human diseases.

In the last decades have emerged new technological platforms that allow evaluation of genes, transcripts, proteins, or metabolites of a living being, so-called omics sciences. More importantly, new technics for their integration have provided access to a complete set of information of the current conditions and features of a specific biological sample in a precise moment. Thus, omic sciences are now considered an essential tool for patient stratification in base to their severity, to understand disease progression and to identify new biomarkers. Severe patients, that are out of control, provide an excellent model to understand disease evolution and to identify new intervention and biomarkers strategies. Here we discuss the use of metabolomics to understand severity in allergic diseases in a strategy that opens new insights as well as identify new biological systems relevant for allergy progression. Metabolomics strategies are based in parallel evaluation of different allergy severity models by mean of untargeted analysis that allows the identification of potential biomarkers. Overlapping of different biomarkers in multiple models, provides information of general as well as specific biological systems involved in each model. Later a selected panel of biomarkers will be used in a target method to explore the diagnosis potential to stratify allergic patients.

Metabolomics, understood as a data driven strategy trying to find markers of a situation under study without a priori hypothesis, has rapidly caught the attention and evolved from the simple pattern recognition strategy, which was a great innovation at its origins, to the interest for the final identification of markers responsible for class separation, i.e., from data to knowledge. Due to differences in physico-chemical properties and concentrations of the metabolites, but also due to differences in matrix properties, crossplatform approaches are proving to increase the capability of information. Once more techniques do not compete. This is the scene where capillary electrophoresis (CE) has its niche to provide information mainly on polar or ionic compounds in biological fluids. General advantages and disadvantages of CE for sample fingerprinting will be discussed and methods will be classified depending on the detection system (UV or MS) as this strongly affects all the conditions. Recent developments will be presented in different biological fluids, although urine is without a doubt the preferred sample for CE analysis.