February 2007 Meeting Announcement, Delaware Valley Mass Spectrometry Discussion Group
- Topic: Qualitative and Quantitative DART/MS
Jing-Tao Wu, Ph.D. Millennium Pharmaceuticals, Inc
Chris Petucci, Discovery Analytical Chemistry, Wyeth Research, Collegeville, PA
Jing-Tao Wu, "A New Tool or a New Fantasy: Some Initial Experience and Thoughts on DART for Small Molecule Bioanalysis"
Chris Petucci, "Direct Analysis in Real Time for Fast Reaction Monitoring in Drug Discovery"
- Date: Monday, February 12, 2007. 6:30 PM
- Time: Social Hour: 6:30 PM.
Talk: 7:30 PM.
Please RSVP to Christopher Petucci PETUCCC@wyeth.com by Thursday February 8th.
- Place: Department of Chemistry, Villanova University (Room 154, Mendel Hall)
- "A New Tool or a New Fantasy: Some Initial Experience and Thoughts on DART for Small Molecule Bioanalysis" by Jing-Tao Wu:
The rapid progress made in small molecule bioanalysis during the past decade has enabled ADME function to engage into the drug discovery process to effectively reduce the attrition in drug development. However, as the systemic exposure based attrition in drug development dropped down to almost single digit; the advancement of conventional bioanalysis based on incremental throughput improvement seems to lose momentum. In our opinion, the future growth for bioanalysis as a discipline is to develop enabling technology to address development attritions due to toxicity and lack of efficacy, and in the meantime, to develop tools to simplify the conventional assays and move them to the clinical bedside. As a new ionization tool, DART was brought in for evaluation towards these goals. In this presentation, we will share some perspectives and preliminary results from this effort.
- "Direct Analysis in Real Time for Fast Reaction Monitoring in Drug Discovery" by Chris Petucci:
Direct analysis in real time (DART) is a novel ionization technique that provides for the ionization of compounds under ambient conditions. This technology can be useful in drug discovery for the rapid analysis of hundreds of samples each day.
Several commercially available drug compounds were analyzed by LC/UV/ESI and DART interfaced to a Waters quadrupole MS. The mass spectra obtained by DART/MS for the molecular ions of these compounds agrees with that obtained by LC/UV/ESI-MS. The main difference between these techniques was that a few dozen compounds could be analyzed by DART/MS within 10 minutes while the LC/UV/ESI-MS experiments took more than 1.5 hours.
DART/MS was also examined to determine if it could be used to monitor synthetic organic reactions in drug discovery and for the molecular weight confirmation of final products. For simple reaction monitoring, the trends in mass spectral signals for the reactant and product obtained using DART/MS scale with those of the diode array or the total ion chromatogram obtained by LC/UV/ESI-MS. However, complex reaction mixtures could not be successfully monitored using DART/MS. In general, DART is a new ionization tool to complement LC/UV/ESI-MS for the rapid characterization of compounds in drug discovery.
- Jing-Tao Wu is the Director of the bioanalytical group in the Drug Metabolism and Pharmacokinetics Department of Millennium Pharmaceuticals, Inc. In this role, he leads the bioanalytical group to provide mass spectrometry based bioanalytical support for all discovery and development projects. He is also responsible for the overall DMPK activities for multiple development candidates in the pipeline. Before joining Millennium, Jing-Tao worked in the DMPK Department of DuPont Pharmaceuticals as a Senior Research Scientist. He has published over 40 papers in peer reviewed journals in the field of bioanalytical mass spectrometry and drug metabolism and pharmacokinetics. Jing-Tao received his Ph.D. in Analytical Chemistry from the University of Michigan.
- Chris Petucci received a B.S. in Chemistry from Juniata College, an M.S. in Analytical Chemistry from Bucknell University, and a Ph.D. in Analytical Chemistry under Professor Hilkka Kenttämaa at Purdue University. His thesis work focused on ion-molecule reactions to characterize diastereomers and hydrogen atom abstraction reactions of charged, heterocyclic mono- and biradicals related to enediyne antitumor drugs using FT-ICR. Chris is currently a mass spectrometry researcher in drug discovery at Wyeth Research in Collegeville, PA.
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