Analytical and Bioanalytical Chemistry

, Volume 410, Issue 25, pp 6353–6359 | Cite as

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

  • Johannes Schlecht
  • Kevin Jooß
  • Christian NeusüßEmail author


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.


Capillary electrophoresis Electrospray ionization Two-dimensional separation Interference-free mass spectrometry Pharmaceutical analysis 2D interface 



Two dimensional


Ascorbic acid


Affinity capillary electrophoresis


Atmospheric pressure chemical ionization


Atmospheric pressure photo ionization


Acetylsalicylic acid


Background electrolyte




Capillary electrophoresis


Capillary sieving electrophoresis


Capillary isoelectric focusing


Capillary zone electrophoresis


Electrospray ionization


Inductive-coupled plasma


Monoclonal antibody


Matrix-assisted-laser desorption/ionization


Micellar electrokinetic chromatography


Mass spectrometry


Sodium dodecyl sulfate


Funding information

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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Johannes Schlecht
    • 1
    • 2
  • Kevin Jooß
    • 1
    • 3
  • Christian Neusüß
    • 1
    Email author
  1. 1.Faculty of ChemistryAalen UniversityAalenGermany
  2. 2.Pharmaceutical/Medicinal Chemistry, Institute of PharmacyFriedrich-Schiller-University JenaJenaGermany
  3. 3.Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum MünchenNeuherbergGermany

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