Combined untargeted and targeted fingerprinting by comprehensive two-dimensional gas chromatography: revealing fructose-induced changes in mice urinary metabolic signatures

Davide Bressanello, Erica Liberto, Massimo Collino, Fausto Chiazza, Raffaella Mastrocola, Stephen E. Reichenbach, Carlo Bicchi, Chiara Cordero

Research output: Contribution to journalArticle

8 Scopus citations


This study exploits the information potential of comprehensive two-dimensional gas chromatography configured with a parallel dual secondary column-dual detection by mass spectrometry and flame ionization (GC×2GC-MS/FID) to study changes in urinary metabolic signatures of mice subjected to high-fructose diets. Samples are taken from mice fed with normal or fructose-enriched diets provided either in aqueous solution or in solid form and analyzed at three stages of the dietary intervention (1, 6, and 12 weeks). Automated Untargeted and Targeted fingerprinting for 2D data elaboration is adopted for the most inclusive data mining of GC×GC patterns. The UT fingerprinting strategy performs a fully automated peak-region features fingerprinting and combines results from pre-targeted compounds and unknowns across the sample-set. The most informative metabolites, with statistically relevant differences between sample groups, are obtained by unsupervised multivariate analysis (MVA) and cross-validated by multi-factor analysis (MFA) with external standard quantitation by GC-MS. Results indicate coherent clustering of mice urine signatures according to dietary manipulation. Notably, the metabolite fingerprints of mice fed with liquid fructose exhibited greater derangement in fructose, glucose, citric, pyruvic, malic, malonic, gluconic, cis-aconitic, succinic and 2-keto glutaric acids, glycine acyl derivatives (N-carboxy glycine, N-butyrylglycine, N-isovaleroylglycine, N-phenylacetylglycine), and hippuric acid. Untargeted fingerprinting indicates some analytes which were not a priori pre-targeted which provide additional insights: N-acetyl glucosamine, N-acetyl glutamine, malonyl glycine, methyl malonyl glycine, and glutaric acid. Visual features fingerprinting is used to track individual variations during experiments, thereby extending the panorama of possible data elaboration tools.

Original languageEnglish (US)
Pages (from-to)2723-2737
Number of pages15
JournalAnalytical and Bioanalytical Chemistry
Issue number11
StatePublished - Apr 1 2018



  • Comprehensive two-dimensional gas chromatography-mass spectrometry
  • Fructose-induced metabolic derangements
  • Parallel dual secondary column-dual detection
  • Untargeted and targeted fingerprinting
  • Urine metabolic profiling

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry

Cite this