Application of capillary electrophoresis-mass spectrometry for determining organic food contaminants and residues

Food contamination continues to be a serious problem around the world. Surveillance of chemical contaminants in foods is important not only for public health but also because of the negative economic impact of contamination. From the analytical perspective, analysis of contaminants in food is an extremely challenging area. There is a wide variety of questions, ranging from the quantification of extremely low levels of individual components to the detailed assessment and evaluation of the analytical technique possibilities. This review considers the applications of CE coupled to MS detection (CE-MS) for the analysis of organic contaminants in food. Analytical information on sample concentration techniques, as well as on the CE separation conditions and recoveries obtained from water and food are provided. Different sections include several fields of application, such as pesticides, drug residues, or toxic formed during food processing in different matrices. A number of tables report a comprehensive listing of CE-MS applications. As a result, this work presents an update overview on the principal application of CE-MS together with a discussion of their main advantages and drawbacks, and an outline of future trends on analysis of organic contaminants.     

Capillary electrophoresis-mass spectrometry, an attractive tool for drug bioanalysis and biomarker discovery

The coupling of CE with MS detection, a relatively recent hyphenated technique, has gained increasing respect in the field of bioanalytical applications over the past few years. The first part of this review presents CE-MS applications dealing with drug bioanalysis, including forensic analysis and metabolism studies. Practical considerations to achieve a robust and sensitive CE-MS coupling are also presented. It is indeed essential to strictly control some critical electrospray parameters, such as the sheath liquid composition and flow rate, the nebulizing gas pressure as well as the capillary outlet position. The second part of the review critically describes the applications of CE coupled on-line to MS for the identification of biomarkers in body fluids for diagnostic purposes. Since the sample preparation procedures strongly differ according to the intended use (drug bioanalysis or biomarker discovery), they are discussed separately, taking into account the particular properties of plasma and urine matrices.     

Capillary electrophoresis coupled to mass spectrometry for clinical diagnostic purposes

The introduction of fast, sensitive, and robust techniques for proteomic analysis into clinical practice represents a major step toward a new diagnostic approach of body fluids. In addition, proteomics emerges as a key technology for the discovery of disease biomarkers in various body fluids. However, even in relatively protein-deprived body fluids such as urine, the complexity and wide dynamic range of protein expression pose a considerable challenge to both separation and identification technologies. In the present review we discuss from a clinical point-of-view recent advances of the use of proteomics in clinical diagnosis as well as therapy evaluation. We focus on capillary electrophoresis coupled to mass spectrometry (CE-MS) and discuss CE-MS from an application point of view evaluating its merits and vices with regard to biomarker discovery. This review further presents examples of clinical applications of CE-MS for detection and identification of biomarkers in urine.     

2020年毛细管电泳技术年度回顾

该文为2020年毛细管电泳(capillary electrophoresis, CE)技术年度回顾。归纳总结了以“capillary electrophoresis-mass spectrometry”或“capillary isoelectric focusing”或“micellar electrokinetic chromatography”或“capillary electrophoresis”为关键词在ISI Web of Science数据库中进行主题检索得到的2020年CE技术相关研究论文222篇,以及中文期刊《分析化学》和《色谱》中CE技术相关的研究论文37篇。对2020年影响因子(IF)≥5.0的Analytical Chemistry, Food Chemistry, Analytica Chimica Acta和Talanta等13本期刊的38篇文章报道的科研工作作了逐一介绍;对IF<5.0的期刊中CE技术报道较为集中的Journal of Chromatography A和Electrophoresis两本分析化学类期刊发表40篇文章中的代表性内容作了综合介绍;对重要的中文期刊《分析化学》出版的“核酸适配体专刊”和《色谱》出版的2期CE技术专刊所收录的37篇文章中的工作作了总体介绍。总体来说,2020年CE技术发展趋势仍以毛细管电泳-质谱(CE-MS)的新方法和新应用最为突出,主要集中在CE-MS与电化学检测、固相萃取以及多种毛细管电泳模式的联用方面,CE-MS接口相关的报道较前几年有所减少;常规CE技术则以胶束电动毛细管色谱(MEKC)在复杂样本分析、浓缩富集应用为主,尤其在食品和药品等复杂基质样本分析方面的报道较为集中;此外,我国CE相关领域专家学者的科研成果涵盖了CE在生命科学、临床医学、医药研发、环境科学、天然产物、食品分析等领域的应用,代表了国内CE科研应用水平和现状。     

Analysis of nucleic acid constituents by on-line capillary electrophoresis-mass spectrometry

This review is focused on the capillary electrophoresis-mass spectrometric (CE-MS) analysis of nucleic acid constituents in the broadest sense, going from nucleotides and adducted nucleotides over nucleoside analogues to oligonucleotides. These nucleic acid constituents play an important role in a variety of biochemical processes. Hence, their isolation, identification, and quantification will undoubtedly help reveal the process of life and disease mechanisms, such as carcinogenesis, and can also be useful for antitumor and antiviral drug research to provide valuable information about mechanism of action, pharmacokinetics, pharmacodynamics, toxicity, therapeutic drug level monitoring, and quality control related to this substance class. Fundamental investigations into their structure, the search for modifications, the occurrence and biochemical impact of structural variation amongst others, are therefore of great value. In view of the related bioanalytical procedures, the coupling of CE to MS has emerged as a powerful tool for the analysis of the complex mixtures of nucleic acid constituents: CE confers rapid analysis and efficient resolution, while MS provides high selectivity and sensitivity with structural characterization of minute amounts of compound. After an introduction about the biochemical and analytical perspectives on the nucleic acid constituents, the different modes of CE used in this field of research as well as the relevant CE-MS interfaces and the difficulties associated with quantitative CE-MS are briefly discussed. A large section is finally devoted to field-oriented applications.     

CE-MS for metabolomics: Developments and applications in the period 2008-2010

This review provides an update of the state-of-the-art of CE-MS for metabolomic purposes, covering the scientific literature from July 2008 to June 2010. This review describes the different analytical aspects with respect to non-targeted and targeted metabolomics and the new technological developments used in CE-MS for metabolomics. The applicability of CE-MS in metabolomics research is illustrated by examples of the analysis of biomedical and clinical samples, and for bacterial and plant extracts. The relevant papers on CE-MS for metabolomics are comprehensively summarized in a table, including, e.g. information on sample type and pretreatment, and MS detection mode. Future considerations such as challenges for large-scale and (quantitative) clinical metabolomics studies and the use of sheathless interfacing and different ionization techniques are discussed.     

Capillary electrophoresis-mass spectrometry: recent advances to the analysis of small achiral and chiral solutes

We describe here the state-of-the-art development of on-line capillary electrophoresis-mass spectrometry (CE-MS) over the last two years. Technological developments included are novel designs of new interfaces and ionization sources, new capillary coatings, buffers, and micelles as well as application of various modes of CE-MS published in the recent literature. The areas of CE-MS application in analysis of small achiral and chiral solutes are covered in sections that highlight the recent advances and possibilities of each mode of CE-MS. Application areas reviewed in this paper include achiral and chiral pharmaceuticals, agrochemicals, carbohydrates, and small peptides. The separation of enantiomers using micellar electrokinetic chromatography (MEKC)-MS with molecular micelles and capillary electrochromatography (CEC)-MS using pack tapered columns appears to provide good tolerance to electrospray stability for routine on-line CE-MS. These two modes seem to be very suitable for sensitive detection of chiral pharmaceuticals in biological samples, but their use will probably increase in the near future. Overall, it seems that one mode of CE-MS, in particular capillary zone electrophoresis (CZE)-MS, is now recognized as established technique for analysis of small charged solutes, but other modes, such as MEKC-MS and CEC-MS, are still within a period of development in terms of both MS-compatible pseudostationary phases and columns as well as applications.     

Overview on advances in capillary electrophoresis-mass spectrometry of carbohydrates: a tabulated review

The increasing interest for carbohydrates as holder of essential bioinformations has boosted their full characterization through analytical techniques. The intent of this review is to summarize the recent trends regarding on-line and off-line CE-MS coupling for carbohydrate analysis. A statistical survey on the articles that use derivatizing agents as well as on the analyzer and type of instrument coupling (i.e. on- or off-line) is depicted. From a general overview it can be concluded that, whereas derivatization might be useful for the detection of neutral carbohydrates improving separation selectivity with volatile buffers and increasing sensitivity of the MS detection, relatively few works with derivatized carbohydrates were found; this was noticed in particular for glycosides and saccharides carrying ionizable groups, which are normally analyzed without any chemical modification. The most applied coupling is the on-line sheath-liquid interface; for on-line applications, ESI is the sole source used, whilst the most common analyzer is the IT. MS(n) is often exploited, as fragmentation increases the achieved structural information. CE-MS turned out to be mainly used for the analysis of carbohydrates in drug development (i.e. study of oligosaccharides from pathogens, carbohydrate-based drugs and drug metabolites), in nutrition and for characterization of glycans from glycoproteins. The reader will find elucidating tables regarding these recent CE-MS applications, including the main information on the analysis conditions. Comments are meant to help the immediate focus on the usefulness of the analytical technique and predict the difficulties found during analysis and, in case, their overcoming.     

毛细管电泳-质谱联用技术的新进展

毛细管电泳-质谱(CE-MS)联用技术综合了CE的高效分离能力、广泛的样品适应性和MS的高灵敏度、可提供结构信息等优势,已发展成为一种重要的分离分析手段。本文对近几年来CE-MS联用接口技术的发展作一简单介绍,并对CE-MS在生命分析、食品药品分析等领域的一些应用进展予以综述。     

Reproducibility Evaluation of Urinary Peptide Detection Using CE-MS

In recent years, capillary electrophoresis coupled to mass spectrometry (CE-MS) has been increasingly applied in clinical research especially in the context of chronic and age-associated diseases, such as chronic kidney disease, heart failure and cancer. Biomarkers identified using this technique are already used for diagnosis, prognosis and monitoring of these complex diseases, as well as patient stratification in clinical trials. CE-MS allows for a comprehensive assessment of small molecular weight proteins and peptides (<20 kDa) through the combination of the high resolution and reproducibility of CE and the distinct sensitivity of MS, in a high-throughput system. In this study we assessed CE-MS analytical performance with regards to its inter- and intra-day reproducibility, variability and efficiency in peptide detection, along with a characterization of the urinary peptidome content. To this end, CE-MS performance was evaluated based on 72 measurements of a standard urine sample (60 for inter- and 12 for intra-day assessment) analyzed during the second quarter of 2021. Analysis was performed per run, per peptide, as well as at the level of biomarker panels. The obtained datasets showed high correlation between the different runs, low variation of the ten highest average individual log2 signal intensities (coefficient of variation, CV < 10%) and very low variation of biomarker panels applied (CV close to 1%). The findings of the study support the analytical performance of CE-MS, underlining its value for clinical application.     

New hyphenated methodologies in high-sensitivity glycoprotein analysis

High-sensitivity glycoprotein analyses are of particular interest in modern biomedical and clinical research, as well as in the development of recombinant protein products. The evolution of new hyphenated methodologies in high-sensitivity glycoprotein analysis is highlighted in this thematic review. These methodologies include, in particular, capillary LC/MALDI/TOF/TOF MS in conjunction with online permethylation platform, and silica-based lectin microcolumns interfaced to MS. The potential of these methodologies in glycomic and glycoproteomic analysis is demonstrated for model glycoproteins as well as total glycomes and glycoproteomes derived from biological samples. Additionally, the applications of CE-MS, CEC, and nanoLC with graphitized carbon in the areas of glycomics and glycoproteomics are described.     

Combining capillary electrophoresis with mass spectrometry for applications in proteomics

Mass spectrometry (MS)-based proteomics is currently dominated by the analysis of peptides originating either from digestion of proteins separated by two-dimensional gel electrophoresis (2-DE) or from global digestion; the simple peptide mixtures obtained from digestion of gel-separated proteins do not usually require further separation, while the complex peptide mixtures obtained by global digestion are most frequently separated by chromatographic techniques. Capillary electrophoresis (CE) provides alternatives to 2-DE for protein separation and alternatives to chromatography for peptide separation. This review attempts to elucidate how the most promising CE modes, capillary zone electrophoresis (CZE) and capillary isoelectric focusing (CIEF), might best be applied to MS-based proteomics. CE-MS interfacing, mass analyzer performance, column coating to minimize analyte adsorption, and sample stacking for CZE are considered prior to examining numerous applications. Finally, multidimensional systems that incorporate CE techniques are examined; CZE often finds use as a fast, final dimension before ionization for MS, while CIEF, being an equilibrium technique, is well-suited to being the first dimension in automated fractionation systems.     

Capillary electrophoresis-mass spectrometry in food analysis

This work provides an updated overview (including works published till June 2004) on the principal applications of capillary electrophoresis-mass spectrometry (CE-MS) together with their main advantages and drawbacks in food science. Thus, analysis of amino acids, peptides, proteins, carbohydrates, or polyphenols by CE-MS in different foods is reviewed. Also, other natural compounds (e.g., alkaloids) and toxins analyzed by CE-MS in foods are revised. Moreover, exogenous substances with a potential risk for human health (e.g., pesticides, drugs) detected in foods by CE-MS are included in this work. The usefulness of CE-MS for food analysis and the information that this coupling can provide in terms of processing, composition, authenticity, quality, or safety of foods is also discussed.     

Recent advances in the application of capillary electromigration methods for food analysis and Foodomics

The analysis of food components using capillary electromigration methods is reviewed in this work. Papers that were published from February 2009 to February 2011 are included following the previous review by Herrero et al. (Electrophoresis, 2010, 31, 205-228). The analysis of amino acids, biogenic amines, peptides, proteins, DNAs, carbohydrates, phenols, polyphenols, pigments, toxins, pesticides, vitamins, additives, small organic and inorganic ions and other compounds found in foods and beverages are reviewed, as well as those applications of CE for monitoring food interactions and food processing. The use of microchips, CE-MS and chiral-CE in food analysis is also discussed as well as other current and foreseen trends in this area of research including new developments in Foodomics.     

Biomarker discovery by CE-MS enables sequence analysis via MS/MS with platform-independent separation

CE-MS is a successful proteomic platform for the definition of biomarkers in different body fluids. Besides the biomarker defining experimental parameters, CE migration time and molecular weight, especially biomarker's sequence identity is an indispensable cornerstone for deeper insights into the pathophysiological pathways of diseases or for made-to-measure therapeutic drug design. Therefore, this report presents a detailed discussion of different peptide sequencing platforms consisting of high performance separation method either coupled on-line or off-line to different MS/MS devices, such as MALDI-TOF-TOF, ESI-IT, ESI-QTOF and Fourier transform ion cyclotron resonance, for sequencing indicative peptides. This comparison demonstrates the unique feature of CE-MS technology to serve as a reliable basis for the assignment of peptide sequence data obtained using different separation MS/MS methods to the biomarker defining parameters, CE migration time and molecular weight. Discovery of potential biomarkers by CE-MS enables sequence analysis via MS/MS with platform-independent sample separation. This is due to the fact that the number of basic and neutral polar amino acids of biomarkers sequences distinctly correlates with their CE-MS migration time/molecular weight coordinates. This uniqueness facilitates the independent entry of different sequencing platforms for peptide sequencing of CE-MS-defined biomarkers from highly complex mixtures.     

Analysis of carboxylic acids in biological fluids by capillary electrophoresis

This review article addresses the different capillary electrophoretic methods that are being used for the study of both short-chain organic acids (including anionic catecholamine metabolites) and fatty acids in biological samples. This work intends to provide an updated overview (including works published until November 2004) on the recent methodological developments and applications of such procedures together with their main advantages and drawbacks. Moreover, the usefulness of CE analysis of organic acids to study and/or monitor different diseases such as diabetes, new-borns diseases or metabolism disorders is examined. The use of microchip devices and CE-MS couplings for organic acid analysis is also discussed.     

Chiral capillary electrophoresis-mass spectrometry: modes and applications

A review is presented to highlight several approaches for coupling capillary electrophoresis (CE) and electrospray ionization-mass spectrometry (ESI-MS) for analysis of chiral compounds. A short discussion of commercially available CE-MS instruments and interface design is followed by a detail review on various modes of chiral CE-MS. In general, for each CE-MS mode, the capabilities, applications and limitations for chiral analysis have been pointed out. The first mode, chiral capillary zone electrophoresis-mass spectrometry (CZE-MS) in which neutral derivatized cyclodextrins (CDs) are used is possible using either column coupling with voltage switching or a partial-filling technique (PFT). However, some applications of direct coupling of CZE-MS mode are also reported. The second mode is a chiral electrokinetic chromatography-mass spectrometry (EKC-MS) in which a charged chiral selector such as a sulfated beta-CD or a vancomycin could be conveniently employed. This is because these chiral selectors have a significantly higher countercurrent electrophoretic mobility which prevents the entrance of these selectors into the mass spectrometer. The combination of counter-migration and PFT demonstrates that this synergism could be successfully applied to chiral analysis of a broader range of compounds. It is well-known that the on-line coupling of micellar electrokinetic chromatography to mass spectrometry (MEKC-MS) is problematic because the high surface activity and nonvolatile nature of conventional surfactant molecules lower the electrospray ionization efficiency. However, a recent report demonstrates that this hyphenation is now possible with the use of molecular micelles. Various MEKC-ESI-MS parameters that can be used to optimize both chiral resolution and ESI response are discussed. Finally, two recent examples that demonstrate the feasibility of using either open-tubular or packed chiral CEC with MS are reviewed. This survey will attempt to cover the state-of-the-art on various modes of CE-MS from 1998 up to 2002.     

Capillary electrophoresis-mass spectrometry for the analysis of intact proteins 2007-2010

CE coupled to MS has proven to be a powerful analytical tool for the characterization of intact proteins, as it combines the high separation efficiency of CE with the selectivity of MS. This review provides an overview of the development and application of CE-MS methods within the field of intact protein analysis as published between January 2007 and June 2010. Ongoing technological developments with respect to CE-MS interfacing, capillary coatings for CE-MS, coupling of CIEF with MS and chip-based CE-MS are treated. Furthermore, CE-MS of intact proteins involving ESI, MALDI and ICP ionization is outlined and overviews of the use of the various CE-MS methods are provided by tables. Representative examples illustrate the applicability of CE-MS for the characterization of proteins, including glycoproteins, biopharmaceuticals, protein-ligand complexes, biomarkers and dietary proteins. It is concluded that CE-MS is a valuable technique with high potential for intact protein analysis, providing useful information on protein identity and purity, including modifications and degradation products.     

Relevance and use of capillary coatings in capillary electrophoresis–mass spectrometry

Over the last two decades, coupled capillary electrophoresis (CE)–mass spectrometry (MS) has developed into a generally accepted technique with a wide applicability. A growing number of CE-MS applications make use of capillaries where the internal wall is modified with surface coating agents. In CE-MS, capillary coatings are used to prevent analyte adsorption and to provide appropriate conditions for CE-MS interfacing. This paper gives an overview of the various capillary coating strategies used in CE-MS. The main attention is devoted to the way coatings can contribute to a proper CE-MS operation. The foremost capillary coating methods are discussed with emphasis on their compatibility with MS detection. The role of capillary coatings in the control of the electroosmotic flow and the consequences for CE-MS coupling are treated. Subsequently, an overview of reported applications of CE-MS employing different coating principles is presented. Selected examples are given to illustrate the usefulness of the coatings and the overall applicability of the CE-MS systems. It is concluded that capillary coatings can enhance the performance and stability of CE-MS systems, yielding a highly valuable and reproducible analytical tool.     

Simplifying capillary electrophoresis-mass spectrometry operation: eliminating capillary derivatization by using self-coating background electrolytes

To simplify capillary electrophoresis-mass spectrometry (CE-MS) operation, a background electrolyte (BGE) containing a polymer additive is introduced that allows the analysis of peptides and protein mixtures in underivatized fused-silica capillaries without any pretreatment, thereby increasing throughput. The most important characteristic of these polymer additives is that they do not significantly suppress the signals of the proteins and peptides under electrospray ionization, thereby allowing them to be used as an additive to common BGEs that are used for CE-MS analysis of peptide and protein mixtures. In addition, because the fused-silica capillary inner wall is continuously coated with the polymer additive, migration irreproducibility, due to the degradation of the capillary inner wall coating, under CE-MS is minimized. High sensitivity of detection, migration reproducibility, and ease of fabrication allow CE-MS analyses that require long analysis time, such as (CE-MS/MS)n, to be performed with ease. The utility of this background electrolyte has been demonstrated for the analysis of complex protein digests and intact proteins.