, Volume 1, Issue 1, pp 65–73 | Cite as

Comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry (GC × GC-TOF) for high resolution metabolomics: biomarker discovery on spleen tissue extracts of obese NZO compared to lean C57BL/6 mice

  • Werner Welthagen
  • Robert A. Shellie
  • Joachim Spranger
  • Michael Ristow
  • Ralf Zimmermann
  • Oliver Fiehn

Comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry (GC × GC-TOF) was applied for the analysis of complex metabolite profiles from mouse spleen. The resulting two-dimensional chromatograms proved that mass spectral quality and sensitivity were largely improved by the enhanced resolution and zone compression, which are features of GC × GC operation, when compared to classical one-dimensional GC-TOF methods. The improved peak capacity of GC × GC allowed for peaks to be detected that could previously not be separated in one-dimensional GC. A measure of the combined power of chromatographic and mass spectral deconvolution resolution is called “analytical purity”, with higher values indicating less pure peaks. GC × GC-TOF lead to the detection of 1200 compounds with purity better than 0.2, compared to 500 compounds with purity up to 2.5 in one-dimensional GC-TOF. The compounds identified include many of the compounds previously reported in NMR studies and other methods on mammalian tissues. Spleen samples of several obese NZO mice and lean C57BL/6 control strains were analyzed in order to demonstrate the applicability of GC × GC-TOF for biomarker identification.

Key words

Obesity metabonomics metabolic profiling type 2 diabetes mellitus nutrigenomics 


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Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Werner Welthagen
    • 1
    • 2
  • Robert A. Shellie
    • 3
  • Joachim Spranger
    • 4
    • 5
  • Michael Ristow
    • 4
    • 5
  • Ralf Zimmermann
    • 1
    • 2
    • 6
  • Oliver Fiehn
    • 7
  1. 1.Institute of Ecological ChemistryGSF-Research CentreOberschleißheimGermany
  2. 2.Analytical ChemistryUniversity of AugsburgAugsburgGermany
  3. 3.Max-Planck-Institute of Molecular Plant PhysiologyPotsdamGermany
  4. 4.German Institute of Human NutritionPotsdam-RehbrückeGermany
  5. 5.Charité University MedicineBerlinGermany
  6. 6.BIfA – Bavarian Institute of Applied Environmental Research and TechnologyAugsburgGermany
  7. 7.Genome CenterUniversity of CaliforniaDavisUSA

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