Mass Spectrometry-Based Metabolomics: Accelerating the Characterization of Discriminating Signals by Combining Statistical Correlations and Ultrahigh Resolution
Autor: | Pierre Chaminade, Eric Ezan, Thierry Umbdenstock, Vincent Croixmarie, Jean-Claude Tabet, Christophe Junot, Erwan Werner |
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Rok vydání: | 2008 |
Předmět: |
Male
Spectrometry Mass Electrospray Ionization Chemical ionization Electrospray Chromatography Chemistry Electrospray ionization Analytical chemistry Urinalysis Mass spectrometry Rats Analytical Chemistry Adduct Characterization (materials science) Ion Metabolomics Data Interpretation Statistical Phenobarbital Animals Rats Wistar Chromatography Liquid |
Zdroj: | Analytical Chemistry. 80:4918-4932 |
ISSN: | 1520-6882 0003-2700 |
Popis: | A strategy combining autocorrelation matrices and ultrahigh resolution mass spectrometry (MS) was developed to optimize the characterization of discriminating ions highlighted by metabolomics. As an example, urine samples from rats treated with phenobarbital (PB) were analyzed by ultrahigh-pressure chromatography with two different eluting conditions coupled to time-of-flight mass spectrometric detection in both the positive and negative electrospray ionization modes. Multivariate data analyses were performed to highlight discriminating variables from several thousand detected signals: a few hundred signals were found to be affected by PB, whereas a few tenths of them were linked to its metabolism. Autocorrelation matrices were then applied to eliminate adduct and fragment ions. Finally, the characterization of the ions of interest was performed with ultrahigh-resolution mass spectrometry and sequential MS(n) experiments, by using a LC-LTQ-Orbitrap system. The use of different eluting conditions was shown to drastically impact on the chromatographic retention and ionization of compounds, thus providing a way to obtain more exhaustive metabolic fingerprints, whereas autocorrelation matrices allowed one to focus the identification work on the most relevant ions. By using such an approach, 14 PB metabolites were characterized in rat urines, some of which have not been reported in the literature. |
Databáze: | OpenAIRE |
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