| Abstract
| - We report the direct introduction of biological samplesinto a high-resolution mass spectrometer, the LTQ-Orbitrap, as a fast tool for metabolomic studies. A proof ofconcept study was performed on yeast cell extracts thatwere introduced into the mass spectrometer by using flowinjection analysis, with an acquisition time of 3 min.Typical mass spectra contained a few thousand m/zsignals, 400 of which were found to be analyticallyrelevant (i.e., their intensity was 3-fold higher than thatof the background noise and they occurred in at least 60%of the acquisition profiles under identical experimentalconditions). The method was validated by studies of thematrix effect, linearity, and intra-assay precision. Accuratemass measurements in the Orbitrap discriminated between isobaric ions and also indicated the elementalcomposition of the ions of interest with mass errors below5 ppm, for identification purposes. The proposed structures were then assessed by MSn experiments via thelinear ion trap, together with accurate mass determinationof the product ions in the Orbitrap analyzer. When appliedto the study of cadmium toxicity, the method was aseffective as that initially developed by using LC/ESI-MS/MS for a targeted approach. The same metabolic fingerprints were also subjected to multivariate statisticalanalyses. The results highlighted a reorganization of aminoacid metabolism under cadmium conditions in order toincrease the biosynthesis of glutathione.
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