Dr Lekha Sleno
Assistant Professor, Faculty of Sciences, Chemistry Department, Université du Québec à Montréal
Bioanalytical LC-MS applied to reactive drug metabolites and metabolomics
Our laboratory is involved in developing novel bioanalytical LC-MS methods applied to the analyses of endogenous metabolites (“metabolomics”), reactive drug metabolites and their covalent binding to proteins. The first part of the presentation will describe a strategy for detecting reactive metabolites in vitro using a novel glutathione trapping agent based on mass defect and isotope pattern filtering. Atrazine, a common pesticide, will be shown as an example in the discovery of new reactive metabolites using high-resolution LC-MS. Covalent binding can also be directly assessed by LC-MS following the complete digestion of proteins. In the area of metabolomics, it is generally impossible to analyse all endogenous metabolites in a complex sample. One option is to have a more “targeted metabolite profiling” strategy, focusing on a specific class of molecules that can be compared between biological samples. An example of this will be shown for a recent study on carotenoid profiling in algal samples. Also, an important challenge in metabolomics studies is the analysis of very polar metabolites. Normal aqueous phase chromatography is highly amenable to MS analysis and has been used successfully. An interesting application of phosphorylated compounds will be discussed, as well as a method for assessing perturbations in tryptophan metabolism.