Skip to main content
SpringerLink
Log in

New Advances in Amino Acid Profiling in Biological Samples by Capillary Electrophoresis-Mass Spectrometry

  • Protocol
  • First Online:
Amino Acid Analysis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2030))

Abstract

Capillary electrophoresis-mass spectrometry (CE-MS) offers a high efficiency microseparation platform for amino acid profiling when analyzing volume-restricted biological samples, such as a dried blood spot punch. Direct analysis of amino acids and their analogs is routinely achieved using strongly acidic buffer conditions under positive-ion mode detection with a coaxial sheath liquid interface for electrospray ionization (ESI). New advances in online sample preconcentration, pre-column chemical derivatization, and/or low flow/sheathless CE-MS interface designs can further improve sensitivity while allowing for resolution of amino acid stereoisomers and labile aminothiols with low nanomolar detection limits. Additionally, multiplexed separations in CE-MS based on serial injection of seven or more samples within a single run greatly boosts sample throughput (<2–3 min/sample) without added infrastructure costs while allowing for stringent quality control and signal batch correction. Accurate prediction of the electromigration behavior of amino acids and their analogs offers a convenient approach for structural elucidation that is complementary to high-resolution MS and MS/MS. Simultaneous analysis of amino acids together with other classes of ionic metabolites by CE-MS allows for comprehensive metabolomic screening as required for new advances in clinical medicine, nutritional sciences, and population health.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Jorgenson JW, Lukacs KD (1998) Zone electrophoresis in open-tubular glass capillaries. Anal Chem 53:1298–1302

    Article  Google Scholar 

  2. Zuskova I et al (2006) Determination of limiting mobilities and dissociation constants of 21 amino acids by capillary zone electrophoresis at very low pH. J Chromatogr B 841:129–134

    Article  CAS  Google Scholar 

  3. Britz-McKibbin P et al (1999) Analysis of gamma-carboxyglutamic acid content of protein, urine and plasma by capillary electrophoresis and laser-induced fluorescence. Anal Chem 71:1633–1637

    Article  CAS  Google Scholar 

  4. Creamer JS, Mora MF, Willis PA (2017) Enhanced resolution of chiral amino acids with capillary electrophoresis for biosignature detection in extraterrestrial samples. Anal Chem 89:1329–1337

    Article  CAS  Google Scholar 

  5. Prior A et al (2018) Chiral capillary electrophoresis with UV-excited fluorescence detection for the enantiomeric analysis of 9-fluorenylmethoxycarbonyl-derivatized amino acids. Anal Bioanal Chem 410:4979–4990

    Article  CAS  Google Scholar 

  6. Ptolemy AS, Britz-McKibbin P (2006) Sample preconcentration with chemical derivatization by capillary electrophoresis: capillary as preconcentrator, microreactor and chiral selector for high-throughput metabolite screening. J Chromatogr A 1106:7–18

    Article  CAS  Google Scholar 

  7. Poinsot V et al (2014) Recent advances in amino acid analysis by capillary electromigration methods, 2013–2015. Electrophoresis 37:142–161

    Article  Google Scholar 

  8. Soga T et al (2004) Qualitative and quantitative analysis of amino acids by capillary electrophoresis-electrospray ionization-tandem mass spectrometry. Electrophoresis 25:1964–1972

    Article  CAS  Google Scholar 

  9. Maxwell JE, Chen DDY (2008) Twenty years of interface development for capillary electrophoresis-electrospray ionization-mass spectrometry. Anal Chim Acta 627:25–33

    Article  CAS  Google Scholar 

  10. Maxwell EJ, Zhong X, Chen DDY (2010) Asymmetrical emitter geometries for increased range of stable electrospray flow rates. Anal Chem 82:8377–8381

    Article  CAS  Google Scholar 

  11. Hirayama A, Tomita M, Soga T (2012) Sheathless capillary electrophoresis-mass spectrometry with a high-sensitivity porous sprayer for cationic metabolome analysis. Analyst 137:5026–5033

    Article  CAS  Google Scholar 

  12. Sun L et al (2015) A third generation electrokinetically pumped sheath flow nanospray interface with improved sensitivity for automated capillary zone electrophoresis-mass spectrometry analysis of complex proteome digests. J Proteome Res 14:2312–2321

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  14. D’Agostino LA et al (2011) Comprehensive plasma thiol redox status determination for metabolomics. J Proteome Res 10:592–603

    Article  Google Scholar 

  15. Chalcraft KR, Britz-McKibbin P (2009) Newborn screening of inborn errors of metabolism by CE-ESI-MS: a second-tier method with improved specificity and sensitivity. Anal Chem 81:307–314

    Article  CAS  Google Scholar 

  16. Lee R, Niewzcas L, Britz-McKibbin P (2007) Integrative metabolomics for characterizing unknown low-abundance metabolites by capillary electrophoresis-mass spectrometry with computer simulations. Anal Chem 79:403–415

    Article  CAS  Google Scholar 

  17. Sugimoto M et al (2010) Prediction of metabolite identity from accurate mass, migration time prediction and isotopic pattern information in CE-TOF/MS data. Electrophoresis 31:2311–2318

    Article  CAS  Google Scholar 

  18. Onjiko RM et al (2015) Single-cell mass spectrometry reveals small molecules that affect cell fates in the 16-cell embryo. Proc Natl Acad Sci U S A 112:6545–6550

    Article  CAS  Google Scholar 

  19. 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:e0191230

    Article  Google Scholar 

  20. Kuehnbaum NL et al (2013) New advances in separation science for metabolomics: resolving chemical diversity in a post-genomic era. Chem Rev 113:2437–2468

    Article  CAS  Google Scholar 

  21. Williams BJ et al (2007) Amino acid profiling in plant cell cultures: an inter-laboratory comparison of CE-MS and GC-MS. Electrophoresis 28:1371–1379

    Article  CAS  Google Scholar 

  22. Li X et al (2013) Fast quantification of amino acids by microchip electrophoresis-mass spectrometry. Anal Bioanal Chem 405:8131–8136

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  24. Kuehnbaum NJ et al (2014) Personalized metabolomics for predicting glucose tolerance changes in sedentary women after high-intensity interval training. Sci Rep 4:6166

    Article  CAS  Google Scholar 

  25. 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 89:8112–8121

    Article  CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  27. Nori de Macedo A et al (2017) Characterization of the sweat metabolome in screen-positive cystic fibrosis infants: revealing mechanisms beyond impaired chloride transport. ACS Centr Sci 3:904–914

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  30. Desiderio C et al (2010) Capillary electrophoresis-mass spectrometry for the analysis of amino acids. J Sep Sci 33:2385–2393

    Article  CAS  Google Scholar 

  31. Lee R, Britz-McKibbin P (2009) Differential rates of glutathione oxidation for assessment of cellular redox status and antioxidant capacity by capillary electrophoresis-mass spectrometry: an elusive biomarker of oxidative stress. Anal Chem 81:7047–7056

    Article  CAS  Google Scholar 

  32. Lee R et al (2010) Differential metabolomics for quantitative assessment of oxidative stress and nutritional intervention with strenuous exercise: thiol-specific regulation of cellular metabolism with N -acetyl-L cysteine pretreatment. Anal Chem 82:2959–2968

    Article  CAS  Google Scholar 

  33. Giuffrida A et al (2009) Modified cyclodextrins for fast and sensitive chiral-capillary electrophoresis-mass spectrometry. Electrophoresis 30:1734–1742

    Article  CAS  Google Scholar 

  34. Prior A et al (2016) Enantioselective capillary electrophoresis-mass spectrometry of amino acids in cerebrospinal fluid using a chiral derivatizing agent and volatile surfactant. Anal Chim Acta 940:150–158

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The author wishes to acknowledge funding support from the National Science and Engineering Research Council of Canada, Cystic Fibrosis Canada, and Genome Canada.

Author information

Authors and Affiliations

  1. Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada

    Meera Shanmuganathan & Philip Britz-McKibbin

Authors
  1. Meera Shanmuganathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Philip Britz-McKibbin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Philip Britz-McKibbin .

Editor information

Editors and Affiliations

  1. Office of Policy for Pharmaceutical Quality Office of Pharmaceutical Quality, Center for Drug Evaluation and Research US FDA, Silver Spring, MD, USA

    Michail A. Alterman

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Shanmuganathan, M., Britz-McKibbin, P. (2019). New Advances in Amino Acid Profiling in Biological Samples by Capillary Electrophoresis-Mass Spectrometry. In: Alterman, M. (eds) Amino Acid Analysis. Methods in Molecular Biology, vol 2030. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9639-1_25

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-9639-1_25

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9638-4

  • Online ISBN: 978-1-4939-9639-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation