Robert T. Kennedy, Ph.D.


LC-MS for Dynamic Metabolomics of the Brain.

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 T. Kennedy

Robert T. Kennedy, Ph.D.


Professional Preparation
Undergraduate Institution:    University of Florida                                                    B.S., 1984

Graduate Institution:             University of North Carolina-Chapel Hill                    Ph.D., 1988

Post-Doctoral Research:        University of North Carolina-Chapel Hill                    1988-1991


8/2015-present         Chair, Chemistry Department, University of Michigan

8/2002 – present       Hobart H. Willard Distinguished University Professor of Chemistry, University of Michigan

8/2002 – present        Professor of Pharmacology, University of Michigan

8/1998 – 7/2002        Professor of Chemistry, University of Florida

8/1996 – 8/1998        Associate Professor of Chemistry, University of Florida

8/1991 – 8/1996        Assistant Professor of Chemistry, University of Florida


Research Interests

Bioanalytical chemistry. Development of microfluidics, chromatography, electrophoresis, and mass spectrometry methods and instruments. Application of methods to in vivo neuroscience, hormone secretion, metabolomics, high-throughput screening, and enzyme evolution.


Other Experience and Service

  • Scientific Advisory Board of Aclara BioSciences (1995-2000) and CellBiosciences (2002-2007)
  • Member, NIH Study Section (1997-2001)
  • S.Associate Editor, The Analyst (1998-2001)
  • NIH Scientific Review Organization committee (2003)
  • Chair, Gordon Conference on Analytical Chemistry (2003)
  • Conference Advisory Committees for HPLC and ISCC (2005-present)
  • Director of Microfluidics in Biomedical Sciences Training Program (2008-2012)
  • Editor, Journal of Chromatography A (2009)
  • Associate Editor, Analytical Chemistry (2010-)
  • Symposium Chair, HPLC 2016 San Francisco

Honors and Awards

  • ACS Chromatography Award (2017)
  • Ralph Adams Award in Bioanalytical Chemistry (2016)
  • Eastern Analytical Separation Science Award (2012)
  • Golay Award for Lifetime Achievement in Chromatography (2012)
  • McKnight Award for Technical Innovations in Neuroscience (2010)
  • MERIT Award, NIBIB (2008-2018)
  • MERIT Award, NIDDK (2006-2016)
  • AAAS Fellow (2007)
  • American Microchemical Society’s Benedetti-Pichler Memorial Award (2001)
  • NSF Award for Special Creativity (1999-2001)
  • Denise Desty Memorial Award for Most Innovative Paper in Separations (1998)
  • ACS Findeis Award in Analytical Chemistry (1998)
  • University of Florida Research Foundation Professorship (1997-2000)
  • NSF Presidential Faculty Fellow (aka PECASE) (1996-1998)
  • Teaching Improvement Program Award, University of Florida (1995)
  • College of Liberal Arts and Sciences Teacher of the Year Award (1994-1995)
  • Alfred P. Sloan Fellow (1995-1997)
  • Lilly Analytical Research Fellow (1994-1995)
  • Beckman Young Investigator Award (1994-1996)
  • NSF National Young Investigator Award (1993-1996)


Publications (Selected from over 250)

  • Sandlin ZD, Shou MS, Shackman JG, & Kennedy RT (2005) “Microfluidic electrophoresis chip coupled to microdialysis for in vivo monitoring of amino acid neurotransmitters.” Chem. 77:7702-7708.
  • Song P, Mabrouk OS, Hershey ND, & Kennedy RT. (2012) “In vivo neurochemical monitoring using benzoyl chloride derivatization and liquid chromatography mass spectrometry” Chem. 84:412-419.
  • Hamid AA, Pettibone JR, Mabrouk OS, Hetrick VL, Schmidt R, Vander Weele CM, Kennedy RT, Aragona BJ, Berke JD. (2016) “Mesolimbic dopamine signals the value of work” Neuro. 19:117-26.
  • Huang L, Shen H, Atkinson MA, & Kennedy RT (1995) “Detection of exocytosis at individual pancreatic beta-cells by amperometry at a chemically-modified microelectrode.” PNAS 92:9608-9612.
  • Roper MG, Shackman JG, Dahlgren GM, & Kennedy RT (2003) “Microfluidic chip for continuous monitoring of hormone secretion from live cells using an electrophoresis-based immunoassay.” Chem. 75:4711-4717.
  • Gee KR, Zhou ZL, Qian WJ, & Kennedy R (2002) “Detection and imaging of zinc secretion from pancreatic beta-cells using a new fluorescent zinc indicator.” Am. Chem. Soc. 124:776-778.
  • Ueki K, et al. (2006) “Total insulin andIGF-I resistance in pancreatic beta cells causes overt diabetes.” Gen. 38:583-588.
  • Lorenz MA, El Azzouny MA, Kennedy RT, Burant CF. (2013) “Metabolome Response to Glucose in the β-Cell Line INS-1 832/13.” Biol. Chem. 288:10923-35.
  • Schultz, NM, & Kennedy RT, (1993) “Rapid Immunoassays using Capillary Electrophoresis with Fluorescence Detection.” Chem. 65:3161-3165.
  • German I, Buchanan DD, & Kennedy RT (1998) “Aptamers as ligands in affinity probe capillary electrophoresis.” Chem. 70:4540-4545.
  • Jin S, Anderson GJ, Kennedy RT. (2013) “Western blotting using microchip electrophoresis interfaced to a protein capture membrane” Chem. 85:6073-9.
  • Sun S, Slaney TR, & Kennedy RT (2012) “Label free screening of enzyme inhibitors at femtomole scale using segmented flow ESI-MS”, Chem. 84:5794-800.