Ultra-high pressure liquid chromatography apparatus to study the pharmacokinetics of small molecules

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This proposal aims at developing a capacity for the quantification of low-level circulating molecules in biological media. It is intended to support the research of three NSERC-funded research groups with complementary expertise in medicinal chemistry (Marsault), molecular imaging (Lepage) and stem cell research (Bentzinger).******Marsault's research aims at identifying the structural determinants of cellular permeability of macrocycles, a class of molecules that is drawing increasing levels of interest in drug discovery. Toward this end, he modifies macrocyclic peptides to understand how subtle modifications influence their permeability, which is important to further use them as oral drugs. It is equally important to be able to determine the metabolic fate of these molecules.******Bentzinger's research aims at characterizing how muscle stem cells respond and interact with their environment. In that respect, he has identified some key elements of the environment that are important for stem cells fate. He is now in the process of identifying small molecules that influence stem cell fate that will need to be quantified in vivo.******Lepage's research aims to develop better methods for pharmacokinetic modeling of imaging probes used in positron emission tomography and magnetic resonance imaging. In that respect, in order to quantify in vivo the ability of imaging probes to interact with their target, he needs access to an analytical equipment able to quantify low levels of tracers.******The required instrument, a UltraHigh Performance Liquid Chromatography (UPLC) equipped with a UV detector and a fraction collector, will be coupled to an existing tandem MS/MS instrument. The combination of these two instruments will provide the high level of sensibility required to analyze very low levels of compounds in biological fluids. This capacity is critical to support the programs of the three co-applicants, as well as additional collaborations with academic and industrial groups. This expertise is also critical for the training of highly qualified personnel in a context where biological sciences rely more and are heavily on high performance analytical capacities.