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Capillary Electrophoresis-Mass Spectrometry for Metabolomics: Possibilities and Perspectives

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Separation Techniques Applied to Omics Sciences

Part of the book series: Advances in Experimental Medicine and Biology ((PMISB,volume 1336))

Abstract

Capillary electrophoresis-mass spectrometry (CE-MS) is a very useful analytical technique for the selective and highly efficient profiling of polar and charged metabolites in a wide range of biological samples. Compared to other analytical techniques, the use of CE-MS in metabolomics is relatively low as the approach is still regarded as technically challenging and not reproducible. In this chapter, the possibilities of CE-MS for metabolomics are highlighted with special emphasis on the use of recently developed interfacing designs. The utility of CE-MS for targeted and untargeted metabolomics studies is demonstrated by discussing representative and recent examples in the biomedical and clinical fields. The potential of CE-MS for large-scale and quantitative metabolomics studies is also addressed. Finally, some general conclusions and perspectives are given on this strong analytical separation technique for probing the polar metabolome.

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Abbreviations

APFO:

Ammonium perfluorooctanoate

BGE:

Background electrolyte

CEC:

Capillary electrochromatography

CE-MS:

Capillary electrophoresis-mass spectrometry

CGE:

Capillary gel electrophoresis

cIEF:

Capillary isoelectric focusing

CZE:

Capillary zone electrophoresis

EOF:

Electro-osmotic flow

HILIC:

Hydrophilic interaction liquid chromatography

ITP:

Isotachophoresis

MEKC:

Micellar electrokinetic chromatography

MSI:

Multi-segment injection

NACE:

Non-aqueous CE

SDS:

Sodium dodecyl sulphate

TOF-MS:

Time-of-flight mass spectrometry

μep:

Electrophoretic mobility

References

  1. Ramautar R et al (2013) Human metabolomics: strategies to understand biology. Curr Opin Chem Biol 17(5):841–846

    Article  CAS  PubMed  Google Scholar 

  2. Wishart DS et al (2018) HMDB 4.0: the human metabolome database for. Nucleic Acids Res 46(D1):D608–D617

    Article  CAS  PubMed  Google Scholar 

  3. Psychogios N et al (2011) The human serum metabolome. PLoS One 6(2):e16957

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Miggiels P et al (2018) Novel technologies for metabolomics: more for less. TrAC Trends Anal Chem 120:115323

    Google Scholar 

  5. Kuehnbaum NL, Britz-McKibbin P (2013) New advances in separation science for metabolomics: resolving chemical diversity in a post-genomic era. Chem Rev 113(4):2437–2468

    Article  CAS  PubMed  Google Scholar 

  6. Kohler I, Giera M (2017) Recent advances in liquid-phase separations for clinical metabolomics. J Sep Sci 40(1):93–108

    Article  CAS  PubMed  Google Scholar 

  7. Gika HG et al (2014) Current practice of liquid chromatography-mass spectrometry in metabolomics and metabonomics. J Pharm Biomed Anal 87:12–25

    Article  CAS  PubMed  Google Scholar 

  8. Buscher JM et al (2009) Cross-platform comparison of methods for quantitative metabolomics of primary metabolism. Anal Chem 81(6):2135–2143

    Article  CAS  PubMed  Google Scholar 

  9. Tang DQ et al (2016) HILIC-MS for metabolomics: an attractive and complementary approach to RPLC-MS. Mass Spectrom Rev 35(5):574–600

    Article  CAS  PubMed  Google Scholar 

  10. Fukai K et al (2016) Metabolic profiling of total physical activity and sedentary behavior in community-dwelling men. PLoS One 11(10):e0164877

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Harada S et al (2018) Reliability of plasma polar metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry. PLoS One 13(1):e0191230

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Soga T et al (2003) Quantitative metabolome analysis using capillary electrophoresis mass spectrometry. J Proteome Res 2(5):488–494

    Article  CAS  PubMed  Google Scholar 

  13. Kok MGM, Somsen GW, de Jong GJ (2014) The role of capillary electrophoresis in metabolic profiling studies employing multiple analytical techniques. TrAC Trends Anal Chem 61:223–235

    Article  CAS  Google Scholar 

  14. Kok MG, Somsen GW, de Jong GJ (2015) Comparison of capillary electrophoresis-mass spectrometry and hydrophilic interaction chromatography-mass spectrometry for anionic metabolic profiling of urine. Talanta 132:1–7

    Article  CAS  PubMed  Google Scholar 

  15. Ramautar R (2017) Resolving volume-restricted metabolomics using Sheathless capillary electrophoresis-mass spectrometry. Lc Gc Europe 30(12):658–661

    CAS  Google Scholar 

  16. Ruta J et al (2010) A systematic investigation of the effect of sample diluent on peak shape in hydrophilic interaction liquid chromatography. J Chromatogr A 1217(52):8230–8240

    Article  CAS  PubMed  Google Scholar 

  17. Ramautar R et al (2011) Metabolic profiling of human urine by CE-MS using a positively charged capillary coating and comparison with UPLC-MS. Mol BioSyst 7(1):194–199

    Article  CAS  PubMed  Google Scholar 

  18. Naz S, Garcia A, Barbas C (2013) Multiplatform analytical methodology for metabolic fingerprinting of lung tissue. Anal Chem 85(22):10941–10948

    Article  CAS  PubMed  Google Scholar 

  19. Ibanez C et al (2012) CE/LC-MS multiplatform for broad metabolomic analysis of dietary polyphenols effect on colon cancer cells proliferation. Electrophoresis 33(15):2328–2336

    Article  CAS  PubMed  Google Scholar 

  20. Klein J et al (2014) Comparison of CE-MS/MS and LC-MS/MS sequencing demonstrates significant complementarity in natural peptide identification in human urine. Electrophoresis 35(7):1060–1064

    Article  CAS  PubMed  Google Scholar 

  21. Drouin N et al (2018) Effective mobility as a robust criterion for compound annotation and identification in metabolomics: toward a mobility-based library. Anal Chim Acta 1032:178–187

    Article  CAS  PubMed  Google Scholar 

  22. Ramautar R, Somsen GW, de Jong GJ (2009) CE-MS in metabolomics. Electrophoresis 30(1):276–291

    Article  CAS  PubMed  Google Scholar 

  23. Ramautar R et al (2011) CE-MS for metabolomics: developments and applications in the period 2008-2010. Electrophoresis 32(1):52–65

    Article  CAS  PubMed  Google Scholar 

  24. Ramautar R, Somsen GW, de Jong GJ (2013) CE-MS for metabolomics: developments and applications in the period 2010–2012. Electrophoresis 34(1):86–98

    Article  CAS  PubMed  Google Scholar 

  25. Ramautar R, Somsen GW, de Jong GJ (2015) CE-MS for metabolomics: developments and applications in the period 2012–2014. Electrophoresis 36(1):212–224

    Article  CAS  PubMed  Google Scholar 

  26. Ramautar R, Somsen GW, de Jong GJ (2017) CE-MS for metabolomics: developments and applications in the period 2014–2016. Electrophoresis 38(1):190–202

    Article  CAS  PubMed  Google Scholar 

  27. Ramautar R, Somsen GW, de Jong GJ (2019) CE-MS for metabolomics: developments and applications in the period 2016–2018. Electrophoresis 40(1):165–179

    Article  CAS  PubMed  Google Scholar 

  28. Ramautar R (2016) Capillary electrophoresis-mass spectrometry for clinical metabolomics. Adv Clin Chem 74:1–34

    Article  CAS  PubMed  Google Scholar 

  29. Jellum E, Thorsrud AK, Time E (1991) Capillary electrophoresis for diagnosis and studies of human disease, particularly metabolic disorders. J Chromatogr 559(1–2):455–465

    Article  CAS  PubMed  Google Scholar 

  30. Jellum E et al (1997) Diagnostic applications of chromatography and capillary electrophoresis. J Chromatogr B Biomed Sci Appl 689(1):155–164

    Article  CAS  PubMed  Google Scholar 

  31. Jellum E, Dollekamp H, Blessum C (1996) Capillary electrophoresis for clinical problem solving: analysis of urinary diagnostic metabolites and serum proteins. J Chromatogr B Biomed Appl 683(1):55–65

    Article  CAS  PubMed  Google Scholar 

  32. Barbas C et al (1998) Quantitative determination of short-chain organic acids in urine by capillary electrophoresis. Clin Chem 44(6 Pt 1):1340–1342

    Article  CAS  PubMed  Google Scholar 

  33. Mayboroda OA et al (2007) Amino acid profiling in urine by capillary zone electrophoresis – mass spectrometry. J Chromatogr A 1159(1–2):149–153

    Article  CAS  PubMed  Google Scholar 

  34. Soga T et al (2002) Simultaneous determination of anionic intermediates for Bacillus subtilis metabolic pathways by capillary electrophoresis electrospray ionization mass spectrometry. Anal Chem 74(10):2233–2239

    Article  CAS  PubMed  Google Scholar 

  35. Moreno-Gonzalez D et al (2013) Micellar electrokinetic chromatography-electrospray ionization mass spectrometry employing a volatile surfactant for the analysis of amino acids in human urine. Electrophoresis 34(18):2615–2622

    Article  CAS  PubMed  Google Scholar 

  36. Wu Q et al (2014) Pressurized CEC coupled with QTOF-MS for urinary metabolomics. Electrophoresis 35(17):2470–2478

    Article  CAS  PubMed  Google Scholar 

  37. Silvertand LH et al (2008) Recent developments in capillary isoelectric focusing. J Chromatogr A 1204(2):157–170

    Article  CAS  PubMed  Google Scholar 

  38. Huhn C et al (2010) Relevance and use of capillary coatings in capillary electrophoresis-mass spectrometry. Anal Bioanal Chem 396(1):297–314

    Article  CAS  PubMed  Google Scholar 

  39. Ramautar R (2018) Chapter 3 Capillary electrophoresis–mass spectrometry using non-covalently coated capillaries for metabolic profiling of biological samples. In Capillary electrophoresis–mass spectrometry for metabolomics 2018, The Royal Society of Chemistry, pp 53–65

    Google Scholar 

  40. Ramautar R (2018) Chapter 4 Capillary electrophoresis–mass spectrometry for metabolomics using new interfacing designs. In Capillary electrophoresis–mass spectrometry for metabolomics 2018, The Royal Society of Chemistry, pp 66–82

    Google Scholar 

  41. Zhao SS et al (2012) Capillary electrophoresis-mass spectrometry for analysis of complex samples. Proteomics 12(19–20):2991–3012

    Article  CAS  PubMed  Google Scholar 

  42. Hirayama A, Wakayama M, Soga T (2014) Metabolome analysis based on capillary electrophoresis-mass spectrometry. TrAC Trends Anal Chem 61:215–222

    Article  CAS  Google Scholar 

  43. Drouin N, Rudaz S, Schappler J (2018) New supported liquid membrane for electromembrane extraction of polar basic endogenous metabolites. J Pharm Biomed Anal 159:53–59

    Article  CAS  PubMed  Google Scholar 

  44. Smith RD, Udseth HR (1988) Capillary zone electrophoresis-MS. Nature 331(6157):639–640

    Article  CAS  PubMed  Google Scholar 

  45. Klampfl CW (2008) Special issue: capillary electrophoresis-mass spectrometry. Electrophoresis 29(10):1955

    Article  CAS  PubMed  Google Scholar 

  46. Miksik I (2019) Coupling of CE-MS for protein and peptide analysis. J Sep Sci 42(1):385–397

    Article  CAS  PubMed  Google Scholar 

  47. Tycova A, Ledvina V, Kleparnik K (2017) Recent advances in CE-MS coupling: instrumentation, methodology, and applications. Electrophoresis 38(1):115–134

    Article  CAS  PubMed  Google Scholar 

  48. Bonvin G, Schappler J, Rudaz S (2012) Capillary electrophoresis-electrospray ionization-mass spectrometry interfaces: fundamental concepts and technical developments. J Chromatogr A 1267:17–31

    Article  CAS  PubMed  Google Scholar 

  49. Wenz C et al (2015) Interlaboratory study to evaluate the robustness of capillary electrophoresis-mass spectrometry for peptide mapping. J Sep Sci 38(18):3262–3270

    Article  CAS  PubMed  Google Scholar 

  50. Ramautar R et al (2008) Capillary electrophoresis-time of flight-mass spectrometry using noncovalently bilayer-coated capillaries for the analysis of amino acids in human urine. Electrophoresis 29(12):2714–2722

    Article  CAS  PubMed  Google Scholar 

  51. Chalcraft KR et al (2009) Virtual quantification of metabolites by capillary electrophoresis-electrospray ionization-mass spectrometry: predicting ionization efficiency without chemical standards. Anal Chem 81(7):2506–2515

    Article  CAS  PubMed  Google Scholar 

  52. Baidoo EE et al (2008) Capillary electrophoresis-fourier transform ion cyclotron resonance mass spectrometry for the identification of cationic metabolites via a pH-mediated stacking-transient isotachophoretic method. Anal Chem 80(9):3112–3122

    Article  CAS  PubMed  Google Scholar 

  53. Ramautar R et al (2012) Enhancing the coverage of the urinary metabolome by Sheathless capillary electrophoresis-mass spectrometry. Anal Chem 84(2):885–892

    Article  CAS  PubMed  Google Scholar 

  54. Causon TJ et al (2014) Addition of reagents to the sheath liquid: a novel concept in capillary electrophoresis-mass spectrometry. J Chromatogr A 1343:182–187

    Article  CAS  PubMed  Google Scholar 

  55. Bonvin G, Rudaz S, Schappler J (2014) In-spray supercharging of intact proteins by capillary electrophoresis-electrospray ionization-mass spectrometry using sheath liquid interface. Anal Chim Acta 813:97–105

    Article  CAS  PubMed  Google Scholar 

  56. Lindenburg PW et al (2015) Developments in interfacing designs for CE-MS: towards enabling tools for proteomics and metabolomics. Chromatographia 78(5–6):367–377

    Article  CAS  Google Scholar 

  57. Maxwell EJ et al (2010) Decoupling CE and ESI for a more robust interface with MS. Electrophoresis 31(7):1130–1137

    Article  CAS  PubMed  Google Scholar 

  58. Lindenburg PW et al (2014) Capillary electrophoresis-mass spectrometry using a flow-through microvial interface for cationic metabolome analysis. Electrophoresis 35(9):1308–1314

    Article  CAS  PubMed  Google Scholar 

  59. Busnel JM et al (2010) High capacity capillary electrophoresis-electrospray ionization mass spectrometry: coupling a porous Sheathless Interface with transient-Isotachophoresis. Anal Chem 82(22):9476–9483

    Article  CAS  PubMed  Google Scholar 

  60. Klampfl CW (2009) CE with MS detection: a rapidly developing hyphenated technique. Electrophoresis 30(Suppl 1):S83–S91

    Article  PubMed  Google Scholar 

  61. Simpson DC, Smith RD (2005) Combining capillary electrophoresis with mass spectrometry for applications in proteomics. Electrophoresis 26(7–8):1291–1305

    Article  CAS  PubMed  Google Scholar 

  62. Hirayama A et al (2018) Development of a sheathless CE-ESI-MS interface. Electrophoresis 39(11):1382–1389

    Article  CAS  PubMed  Google Scholar 

  63. Moini M (2007) Simplifying CE-MS operation. 2. Interfacing low-flow separation techniques to mass spectrometry using a porous tip. Anal Chem 79(11):4241–4246

    Article  CAS  PubMed  Google Scholar 

  64. Zhang W et al (2019) Utility of sheathless capillary electrophoresis-mass spectrometry for metabolic profiling of limited sample amounts. J Chromatogr B Analyt Technol Biomed Life Sci 1105:10–14

    Article  CAS  PubMed  Google Scholar 

  65. Liu JX et al (2014) Analysis of endogenous nucleotides by single cell capillary electrophoresis-mass spectrometry. Analyst 139(22):5835–5842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Genchi G (2017) An overview on D-amino acids. Amino Acids 49(9):1521–1533

    Article  CAS  PubMed  Google Scholar 

  67. Sánchez-López E et al (2016) Enantioseparation of the constituents involved in the phenylalanine-tyrosine metabolic pathway by capillary electrophoresis tandem mass spectrometry. J Chromatogr A 1467:372–382

    Article  PubMed  CAS  Google Scholar 

  68. Lee S et al (2019) Chiral separation of intact amino acids by capillary electrophoresis-mass spectrometry employing a partial filling technique with a crown ether carboxylic acid. J Chromatogr A 1586:128–138

    Article  CAS  PubMed  Google Scholar 

  69. Geiser L, Rudaz S, Veuthey J-L (2005) Decreasing analysis time in capillary electrophoresis: validation and comparison of quantitative performances in several approaches. Electrophoresis 26(12):2293–2302

    Article  CAS  PubMed  Google Scholar 

  70. Geiser L, Rudaz S, Veuthey J-L (2003) Validation of capillary electrophoresis – mass spectrometry methods for the analysis of a pharmaceutical formulation. Electrophoresis 24(17):3049–3056

    Article  CAS  PubMed  Google Scholar 

  71. Kuehnbaum NL, Kormendi A, Britz-McKibbin P (2013) Multisegment injection-capillary electrophoresis-mass spectrometry: a high-throughput platform for metabolomics with high data fidelity. Anal Chem 85(22):10664–10669

    Article  CAS  PubMed  Google Scholar 

  72. DiBattista A et al (2017) High throughput screening method for systematic surveillance of drugs of abuse by multisegment injection-capillary electrophoresis-mass spectrometry. Anal Chem 89(21):11853–11861

    Article  CAS  PubMed  Google Scholar 

  73. DiBattista A et al (2017) Temporal signal pattern recognition in mass spectrometry: a method for rapid identification and accurate quantification of biomarkers for inborn errors of metabolism with quality assurance. Anal Chem 89(15):8112–8121

    Article  CAS  PubMed  Google Scholar 

  74. Azab S, Ly R, Britz-McKibbin P (2019) Robust method for high-throughput screening of fatty acids by multisegment injection-nonaqueous capillary electrophoresis-mass spectrometry with stringent quality control. Anal Chem 91(3):2329–2336

    Article  CAS  PubMed  Google Scholar 

  75. Ouyang Y et al (2018) Negative-ion mode capillary isoelectric focusing mass spectrometry for charge-based separation of acidic oligosaccharides. Anal Chem 91(1):846–853

    Article  PubMed  CAS  Google Scholar 

  76. Portero EP, Nemes P (2019) Dual cationic-anionic profiling of metabolites in a single identified cell in a live Xenopus laevis embryo by microprobe CE-ESI-MS. Analyst 144(3):892–900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Sánchez-López E et al (2019) Sheathless CE-MS based metabolic profiling of kidney tissue section samples from a mouse model of Polycystic Kidney Disease. Sci Rep 9(1):806

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Rochat B (2017) Proposed confidence scale and ID score in the identification of known-unknown compounds using high resolution MS data. J Am Soc Mass Spectrom 28(4):709–723

    Article  CAS  PubMed  Google Scholar 

  79. Sumner LW et al (2007) Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI). Metabolomics 3(3):211–221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. van Rijswijk M et al (2017) The future of metabolomics in ELIXIR [version 2; peer review: 3 approved]. F1000 Research 2017, 6(ELIXIR):1649. https://doi.org/10.12688/f1000research.12342.2

  81. Guijas C et al (2018) METLIN: a technology platform for identifying knowns and unknowns. Anal Chem 90(5):3156–3164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Gonzalez-Pena D et al (2017) Metabolomic fingerprinting in the comprehensive study of liver changes associated with onion supplementation in Hypercholesterolemic Wistar rats. Int J Mol Sci 18(2):267. https://doi.org/10.3390/ijms18020267

  83. Macedo AN et al (2017) The sweat metabolome of screen-positive cystic fibrosis infants: revealing mechanisms beyond impaired chloride transport. ACS Cent Sci 3(8):904–913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Gulersonmez MC et al (2016) Sheathless capillary electrophoresis-mass spectrometry for anionic metabolic profiling. Electrophoresis 37(7–8):1007–1014

    Article  CAS  PubMed  Google Scholar 

  85. Gonzalez-Ruiz V et al (2018) ROMANCE: a new software tool to improve data robustness and feature identification in CE-MS metabolomics. Electrophoresis 39(9–10):1222–1232

    Article  CAS  PubMed  Google Scholar 

  86. Gagnebin Y et al (2019) Toward a better understanding of chronic kidney disease with complementary chromatographic methods hyphenated with mass spectrometry for improved polar metabolome coverage. J Chromatogr B 1116:9–18

    Google Scholar 

  87. Gonzalez-Ruiz V et al (2017) Unravelling the effects of multiple experimental factors in metabolomics, analysis of human neural cells with hydrophilic interaction liquid chromatography hyphenated to high resolution mass spectrometry. J Chromatogr A 1527:53–60

    Article  CAS  PubMed  Google Scholar 

  88. DiBattista A et al (2019) Metabolic signatures of cystic fibrosis identified in dried blood spots for newborn screening without carrier identification. J Proteome Res 18(3):841–854

    CAS  PubMed  Google Scholar 

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Acknowledgements

Dr. Rawi Ramautar would like to acknowledge the financial support of the Vidi grant scheme of the Netherlands Organisation for Scientific Research (NWO Vidi 723.016.003).

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Authors and Affiliations

  1. Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands

    Nicolas Drouin & Rawi Ramautar

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  1. Nicolas Drouin
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  2. Rawi Ramautar
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Correspondence to Rawi Ramautar .

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Editors and Affiliations

  1. Analytical Chemistry Department, University of Campinas, Institute of Chemistry, Campinas, São Paulo, Brazil

    Ana Valéria Colnaghi Simionato

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Drouin, N., Ramautar, R. (2021). Capillary Electrophoresis-Mass Spectrometry for Metabolomics: Possibilities and Perspectives. In: Colnaghi Simionato, A.V. (eds) Separation Techniques Applied to Omics Sciences. Advances in Experimental Medicine and Biology(), vol 1336. Springer, Cham. https://doi.org/10.1007/978-3-030-77252-9_9

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