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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

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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.

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Authors and Affiliations

  1. Institute of Ecological Chemistry, GSF-Research Centre, Oberschleißheim, D-85764, Germany

    Werner Welthagen & Ralf Zimmermann

  2. Analytical Chemistry, University of Augsburg, Augsburg, D-86159, Germany

    Werner Welthagen & Ralf Zimmermann

  3. Max-Planck-Institute of Molecular Plant Physiology, 14424, Potsdam, Germany

    Robert A. Shellie

  4. German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany

    Joachim Spranger & Michael Ristow

  5. Charité University Medicine, Berlin, Germany

    Joachim Spranger & Michael Ristow

  6. BIfA – Bavarian Institute of Applied Environmental Research and Technology, Augsburg, D-86167, Germany

    Ralf Zimmermann

  7. Genome Center, University of California, Davis, CA, 95616-8816, USA

    Oliver Fiehn

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  1. Werner Welthagen
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  2. Robert A. Shellie
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  3. Joachim Spranger
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  4. Michael Ristow
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  6. Oliver Fiehn
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Correspondence to Oliver Fiehn.

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Welthagen, W., Shellie, R.A., Spranger, J. et al. 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. Metabolomics 1, 65–73 (2005). https://doi.org/10.1007/s11306-005-1108-2

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