Skip to main content
Log in

Two-dimensional capillary electrophoresis-mass spectrometry (CE-CE-MS): coupling MS-interfering capillary electromigration methods with mass spectrometry

  • Trends
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Electromigration separation techniques often demand certain compounds in the electrolyte to achieve the required selectivity and efficiency. These compounds, including the electrolyte itself, ampholytes, polymeric compounds for sieving, complexing agents, tensides, etc. are often non-volatile. Thus, interference with the electrospray ionization process is a common issue, impeding direct coupling of such electrolyte systems to mass spectrometry. Still, several options exist to obtain mass spectra after separation, including offline fractionation, alternative ionization, dilution, or the change to volatile constituents. In the first part of this article, these methods are discussed. However, all of these options are a compromise of separation performance and sensitivity of mass spectrometric detection. Two-dimensional capillary electrophoresis-mass spectrometry (CE-CE-MS) systems represent a promising alternative to the aforementioned challenges, as they allow the use of existing methods with best separation performance in combination with sensitive mass characterization. In this context, the second part of this article is dedicated to the advantages, limitations, and applications of this approach. Finally, an outlook towards future developments is given.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

2D:

Two dimensional

AA:

Ascorbic acid

ACE:

Affinity capillary electrophoresis

APCI:

Atmospheric pressure chemical ionization

APPI:

Atmospheric pressure photo ionization

ASA:

Acetylsalicylic acid

BGE:

Background electrolyte

CD:

Cyclodextrin

CE:

Capillary electrophoresis

CSE:

Capillary sieving electrophoresis

CIEF:

Capillary isoelectric focusing

CZE:

Capillary zone electrophoresis

ESI:

Electrospray ionization

ICP:

Inductive-coupled plasma

mAb:

Monoclonal antibody

MALDI:

Matrix-assisted-laser desorption/ionization

MEKC:

Micellar electrokinetic chromatography

MS:

Mass spectrometry

SDS:

Sodium dodecyl sulfate

References

  1. Menzinger F, Schmitt-Kopplin P, Freitag D, Kettrup A. Analysis of agrochemicals by capillary electrophoresis. J Chromatogr A. 2000;891(1):45–67.

    Article  CAS  PubMed  Google Scholar 

  2. Fukushi K, Takeda S, Chayama K, Wakida S-I. Application of capillary electrophoresis to the analysis of inorganic ions in environmental samples. J Chromatogr A. 1999;834(1–2):349–62.

    Article  CAS  PubMed  Google Scholar 

  3. Anastos N, Barnett NW, Lewis SW. Capillary electrophoresis for forensic drug analysis: a review. Talanta. 2005;67(2):269–79.

    Article  CAS  PubMed  Google Scholar 

  4. Frazier RA, Papadopoulou A. Recent advances in the application of capillary electrophoresis for food analysis. Electrophoresis. 2003;24(22–23):4095–105.

    Article  CAS  PubMed  Google Scholar 

  5. Kraly J, Fazal MA, Schoenherr RM, Bonn R, Harwood MM, Turner E, et al. Bioanalytical applications of capillary electrophoresis. Anal Chem. 2006;78(12):4097–110.

    Article  CAS  PubMed  Google Scholar 

  6. Moritz B, Schnaible V, Kiessig S, Heyne A, Wild M, Finkler C, et al. Evaluation of capillary zone electrophoresis for charge heterogeneity testing of monoclonal antibodies. J Chromatogr B Analyt Technol Biomed Life Sci. 2015;983-984:101–10.

    Article  CAS  PubMed  Google Scholar 

  7. Mitnik L, Novotny M, Felten C, Buonocore S, Koutny L, Schmalzing D. Recent advances in DNA sequencing by capillary and microdevice electrophoresis. Electrophoresis. 2001;22(19):4104–17.

    Article  CAS  PubMed  Google Scholar 

  8. Zhu Z, Lu JJ, Liu S. Protein separation by capillary gel electrophoresis: a review. Anal Chim Acta. 2012;709:21–31.

    Article  CAS  PubMed  Google Scholar 

  9. Schmitt-Kopplin P, Frommberger M. Capillary electrophoresis-mass spectrometry: 15 years of developments and applications. Electrophoresis. 2003;24(22–23):3837–67.

    Article  CAS  PubMed  Google Scholar 

  10. Desiderio C, Rossetti DV, Iavarone F, Messana I, Castagnola M. Capillary electrophoresis-mass spectrometry: recent trends in clinical proteomics. J Pharm Biomed Anal. 2010;53(5):1161–9.

    Article  CAS  PubMed  Google Scholar 

  11. Klepárník K. Recent advances in combination of capillary electrophoresis with mass spectrometry: methodology and theory. Electrophoresis. 2015;36(1):159–78.

    Article  CAS  PubMed  Google Scholar 

  12. Monton MRN, Terabe S. Recent developments in capillary electrophoresis-mass spectrometry of proteins and peptides. Anal Sci. 2005;21(1):5–13.

    Article  CAS  PubMed  Google Scholar 

  13. Petersson P, Jörntén-Karlsson M, Stålebro M. Direct coupling of micellar electrokinetic chromatography to mass spectrometry using a volatile buffer system based on perfluorooctanoic acid and ammonia. Electrophoresis. 2003;24(6):999–1007.

    Article  CAS  PubMed  Google Scholar 

  14. van Biesen G, Bottaro CS. Ammonium perfluorooctanoate as a volatile surfactant for the analysis of N-methylcarbamates by MEKC-ESI-MS. Electrophoresis. 2006;27(22):4456–68.

    Article  CAS  PubMed  Google Scholar 

  15. Moreno-González D, Haselberg R, Gámiz-Gracia L, García-Campaña AM, de JGJ, Somsen GW. Fully compatible and ultra-sensitive micellar electrokinetic chromatography-tandem mass spectrometry using sheathless porous-tip interfacing. J Chromatogr A. 2017;1524:283–9.

    Article  CAS  PubMed  Google Scholar 

  16. Tang Q, Harrata AK, Lee CS. Capillary isoelectric focusing-electrospray mass spectrometry for protein analysis. Anal Chem. 1995;67:3515–9.

    Article  CAS  Google Scholar 

  17. Hühner J, Lämmerhofer M, Neusüß C. Capillary isoelectric focusing-mass spectrometry: coupling strategies and applications. Electrophoresis. 2015;36(21–22):2670–86.

    Article  CAS  PubMed  Google Scholar 

  18. Silva M. MEKC: an update focusing on practical aspects. Electrophoresis. 2007;28(1–2):174–92.

    Article  CAS  PubMed  Google Scholar 

  19. Simó C, García-Cañas V, Cifuentes A, CE-MS C. Electrophoresis. 2010;31(9):1442–56.

    PubMed  Google Scholar 

  20. Týčová A, Ledvina V, Klepárník K. Recent advances in CE-MS coupling: instrumentation, methodology, and applications. Electrophoresis. 2017;38(1):115–34.

    Article  CAS  PubMed  Google Scholar 

  21. Lindenburg PW, Haselberg R, Rozing G, Ramautar R. Developments in interfacing designs for CE-MS: towards enabling tools for proteomics and metabolomics. Chroma. 2015;78(5–6):367–77.

    Article  CAS  Google Scholar 

  22. Dai J, Lamp J, Xia Q, Zhang Y. Capillary isoelectric focusing-mass spectrometry method for the separation and online characterization of intact monoclonal antibody charge variants. Anal Chem. 2018;90(3):2246–54.

    Article  CAS  PubMed  Google Scholar 

  23. Stutz H. Advances in the analysis of proteins and peptides by capillary electrophoresis with matrix-assisted laser desorption/ionization and electrospray-mass spectrometry detection. Electrophoresis. 2005;26(7–8):1254–90.

    Article  CAS  PubMed  Google Scholar 

  24. Isoo K, Otsuka K, Terabe S. Application of sweeping to micellar electrokinetic chromatography-atmospheric pressure chemical ionization-mass spectrometric analysis of environmental pollutants. Electrophoresis. 2001;22(16):3426–32.

    Article  CAS  PubMed  Google Scholar 

  25. Mol R, de JGJ, Somsen GW. Atmospheric pressure photoionization for enhanced compatibility in on-line micellar electrokinetic chromatography-mass spectrometry. Anal Chem. 2005;77(16):5277–82.

    Article  CAS  PubMed  Google Scholar 

  26. Chen J, Fu F, Wu S, Wang J, Wang Z. Simultaneous detection of zinc dimethyldithiocarbamate and zinc ethylenebisdithiocarbamate in cabbage leaves by capillary electrophoresis with inductively coupled plasma mass spectrometry. J Sep Sci. 2017;40(19):3898–904.

    Article  CAS  PubMed  Google Scholar 

  27. Malerod H, Lundanes E, Greibrokk T. Recent advances in on-line multidimensional liquid chromatography. Anal Methods. 2010;2(2):110–22.

    Article  CAS  Google Scholar 

  28. Kohl FJ, Montealegre C, Neusüß C. On-line two-dimensional capillary electrophoresis with mass spectrometric detection using a fully electric isolated mechanical valve. Electrophoresis. 2016;37(7–8):954–8.

    Article  CAS  PubMed  Google Scholar 

  29. Helmja K, Borissova M, Knjazeva T, Jaanus M, Muinasmaa U, Kaljurand M, et al. Fraction collection in capillary electrophoresis for various stand-alone mass spectrometers. J Chromatogr A. 2009;1216(17):3666–73.

    Article  CAS  PubMed  Google Scholar 

  30. Kohl FJ, Sánchez-Hernández L, Neusüß C. Capillary electrophoresis in two-dimensional separation systems: techniques and applications. Electrophoresis. 2015;36(1):144–58.

    Article  CAS  PubMed  Google Scholar 

  31. Kler PA, Sydes D, Huhn C. Column-coupling strategies for multidimensional electrophoretic separation techniques. Anal Bioanal Chem. 2015;407(1):119–38.

    Article  CAS  PubMed  Google Scholar 

  32. Neuberger S, Jooß K, Ressel C, Neusüß C. Quantification of ascorbic acid and acetylsalicylic acid in effervescent tablets by CZE-UV and identification of related degradation products by heart-cut CZE-CZE-MS. Anal Bioanal Chem. 2016;408(30):8701–12.

    Article  CAS  PubMed  Google Scholar 

  33. Jooß K, Hühner J, Kiessig S, Moritz B, Neusüß C. Two-dimensional capillary zone electrophoresis-mass spectrometry for the characterization of intact monoclonal antibody charge variants, including deamidation products. Anal Bioanal Chem. 2017;409(26):6057–67.

    Article  CAS  PubMed  Google Scholar 

  34. Hühner J, Neusüß C. CIEF-CZE-MS applying a mechanical valve. Anal Bioanal Chem. 2016;408(15):4055–61.

    Article  CAS  PubMed  Google Scholar 

  35. Hühner J, Jooß K, Neusüß C. Interference-free mass spectrometric detection of capillary isoelectric focused proteins, including charge variants of a model monoclonal antibody. Electrophoresis. 2017;38(6):914–21.

    Article  CAS  PubMed  Google Scholar 

  36. Montealegre C, Neusüß C. Coupling imaged capillary isoelectric focusing with mass spectrometry using a nanoliter valve. Electrophoresis. 2018; https://doi.org/10.1002/elps.201800013

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The authors thank Hoffman-La Roche Ltd. (Basel, Switzerland) for financial support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christian Neusüß.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schlecht, J., Jooß, K. & Neusüß, C. Two-dimensional capillary electrophoresis-mass spectrometry (CE-CE-MS): coupling MS-interfering capillary electromigration methods with mass spectrometry. Anal Bioanal Chem 410, 6353–6359 (2018). https://doi.org/10.1007/s00216-018-1157-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-018-1157-9

Keywords

Navigation