$20 – $55

CCDG February Dinner Lecture: LC-MS for Dynamic Metabolomics of the Brain

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Mickey Finn's Brewery

345 North Milwaukee Avenue

Libertyville, IL 60048

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Complex mixtures, such as those encountered in biology, are often analyzed by LC-MS because of the tremendous resolving power of combining these techniques. Powerful LC-MS platforms have become the norm for metabolomics for example. Even though mass spectrometers are providing ever higher resolution, improved separations are often found to improve the detection of metabolites by reducing ionization suppression and simplifying spectra interpretation. Improving the resolution of HPLC can be achieved by using smaller particles or longer columns. Both approaches require higher pressure for driving mobile phase flow so that pressure available can be considered a limiting factor in resolution. Even with high resolution, the broad polarity range of metabolomics samples makes it difficult to resolve all compounds in a mixture. In this work we describe use of an HPLC system capable of generating 40,000 psi for analysis of metabolomic mixtures. We also describe derivatization strategies that improve separation and detection of polar compounds when using reversed phase columns with ESI-MS. We discuss the use of these methods in monitoring the brain chemistry of living subjects. We show that using microdialysis coupled to LC-MS/MS it is possible detect changes in neurotransmitters and related metabolites associated with disease states, behavior, and drug effects.

Robert Kennedy is the Willard Professor of Chemistry at the University of Michigan. Prof. Kennedy’s research interests are analytical chemistry its application to neuroscience, endocrinology, and biotechnology. A theme of his group has been development of high-speed separations for sensing, detection of non-covalent complexes, and screening. His group has developed instrumentation that couples sampling probes to capillary electrophoresis, capillary chromatography, LC-MS, and microfluidic assays for monitoring neurotransmitters in vivo. These methods have been used for studying changes in neurotransmitter concentrations associated with behavior and diseases. His group has also developed sensors and microfluidic electrophoresis devices for monitoring insulin secretion from pancreatic b-cells. These methods are coupled with LC-MS metabolomics to understand the biochemical mechanism of insulin secretion and perturbations associated with diabetes. His group is also researching use of rapid electrophoretic and mass spectrometric assays for high-throughput screening. His work has been recognized by several awards including McKnight Award for Technical Innovations in Neuroscience, EAS Separation Science Award, Golay Award for Achievements in Chromatography, The Ralph Adams Award in Bioanalytical Chemistry and several teaching awards. He has held several service posts and is presently Associate Editor of Analytical Chemistry and Chair of the Chemistry Department at University of Michigan.

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Mickey Finn's Brewery

345 North Milwaukee Avenue

Libertyville, IL 60048

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