Metabolomics

, Volume 4, Issue 2, pp 128–140

Towards high-throughput metabolomics using ultrahigh-field Fourier transform ion cyclotron resonance mass spectrometry

  • Jun Han
  • Ryan M. Danell
  • Jayanti R. Patel
  • Dmitry R. Gumerov
  • Cameron O. Scarlett
  • J. Paul Speir
  • Carol E. Parker
  • Ivan Rusyn
  • Steven Zeisel
  • Christoph H. Borchers
Original Article

DOI: 10.1007/s11306-008-0104-8

Cite this article as:
Han, J., Danell, R.M., Patel, J.R. et al. Metabolomics (2008) 4: 128. doi:10.1007/s11306-008-0104-8

Abstract

With unmatched mass resolution, mass accuracy, and exceptional detection sensitivity, Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FTICR-MS) has the potential to be a powerful new technique for high-throughput metabolomic analysis. In this study, we examine the properties of an ultrahigh-field 12-Tesla (12T) FTICR-MS for the identification and absolute quantitation of human plasma metabolites, and for the untargeted metabolic fingerprinting of inbred-strain mouse serum by direct infusion (DI). Using internal mass calibration (mass error ≤1 ppm), we determined the rational elemental compositions (incorporating unlimited C, H, N and O, and a maximum of two S, three P, two Na, and one K per formula) of approximately 250 out of 570 metabolite features detected in a 3-min infusion analysis of aqueous extract of human plasma, and were able to identify more than 100 metabolites. Using isotopically-labeled internal standards, we were able to obtain excellent calibration curves for the absolute quantitation of choline with sub-pmol sensitivity, using 500 times less sample than previous LC/MS analyses. Under optimized serum dilution conditions, chemical compounds spiked into mouse serum as metabolite mimics showed a linear response over a 600-fold concentration range. DI/FTICR-MS analysis of serum from 26 mice from 2 inbred strains, with and without acute trichloroethylene (TCE) treatment, gave a relative standard deviation (RSD) of 4.5%. Finally, we extended this method to the metabolomic fingerprinting of serum samples from 49 mice from 5 inbred strains involved in an acute alcohol toxicity study, using both positive and negative electrospray ionization (ESI). Using these samples, we demonstrated the utility of this method for high-throughput metabolomics, with more than 400 metabolites profiled in only 24 h. Our experiments demonstrate that DI/FTICR-MS is well-suited for high-throughput metabolomic analysis.

Keywords

FTICR-MS Metabolomics Direct infusion Plasma Serum 

Supplementary material

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Jun Han
    • 1
    • 2
  • Ryan M. Danell
    • 3
  • Jayanti R. Patel
    • 4
  • Dmitry R. Gumerov
    • 4
  • Cameron O. Scarlett
    • 5
    • 6
    • 7
  • J. Paul Speir
    • 4
  • Carol E. Parker
    • 5
    • 6
  • Ivan Rusyn
    • 2
  • Steven Zeisel
    • 8
  • Christoph H. Borchers
    • 1
    • 5
    • 6
  1. 1.University of Victoria – Genome BC Proteomics CentreVictoriaCanada
  2. 2.Department of Environmental Sciences and Engineering, School of Public HealthUniversity of North CarolinaChapel HillUSA
  3. 3.Danell ConsultingGreenvilleUSA
  4. 4.Bruker Daltonics Inc.BillericaUSA
  5. 5.Department of Biochemistry and BiophysicsUniversity of North CarolinaChapel HillUnited States
  6. 6.UNC-Duke Proteomics CenterUniversity of North CarolinaChapel HillUSA
  7. 7.School of PharmacyUniversity of WisconsinMadisonUSA
  8. 8.Nutrition Research Institute, Department of Nutrition, School of Public HealthUniversity of North CarolinaChapel HillUSA