Profiling of carboxyl-containing metabolites in smokers and non-smokers by stable isotope labeling combined with LC-MS/MS
2019
Abstract Profiling of carboxyl-containing metabolites in smokers and non-smokers provides insight into the smoking-related biological events and causal relationships between exposure and adverse events. However, more comprehensive analysis of carboxyl-containing metabolites in bio-matrices with high sensitivity and accuracy is challenging. In this work, stable isotope labeling in combination with liquid chromatography-tandem mass spectrometry was used for untargeted profiling and relative quantification of carboxyl-containing metabolites in plasma of smokers and non-smokers. A pair of isotope labeling reagents, N , N -dimethylethylenediamine (DMED) and d 4 -DMED was used to label carboxyl-containing metabolites. Since the isotope labeled dimethylamino moieties of DMED and d 4 -DMED are easily fragmented and lost as characteristic neutral fragments of 45 and 49 Da, respectively, double neutral loss scans can be used to profiling of carboxyl-containing metabolites. Subsequently, based on the ion pair parameters obtained from double neutral loss scans, relative quantification method was developed. As a result, 269 carboxyl-containing metabolite candidates were discovered, and 88 metabolite candidates were found to have significant alterations between smokers and non-smokers. 7Z, 10Z-hexadecadienoic acid, myristic acid and 3β-hydroxy-5-cholestenoic acid with significant differences confirmed by standard comparison are linked to smoking related inflammation, abnormal bile acid synthesis and cholesterol metabolism.
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