November 2001 Meeting Announcement, Delaware Valley Mass Spectrometry Discussion Group
- Topic: "High Speed Parallel LC/MS/MS with Integrated Parallel Sample Preparation for Lead Optimization in Drug Discovery"
- Speaker: Jing-Tao Wu, Bristol-Myers Squibb Company
- Date: Monday, November 12, 2001. 6:30 PM
- Time: Social Hour: 6:30 PM. (Pizza and Beer)
Talk: 7:30 PM.
- Place: Widener University, Webb Room.
The optimization of ADME (Absorption, Distribution, Metabolism, and Excretion) properties of new chemical entities plays an important role in the lead optimization process in drug discovery. Most of the screenings for this purpose involve the analysis of samples in various biological matrices using LC/MS/MS technique. Sample clean up or extraction is generally required before analysis. Also, good chromatographic separation is essential to maintaining assay specificity and minimizing matrix effect. Hence, sample extraction and chromatographic separation are two indispensable steps in bioanalysis. New analytical approaches that can provide strategies to enhance and match the throughput of both steps are highly demanded.
During the past a few years, several approaches have been developed in our laboratory to integrate and speed up the chromatographic separation and sample extraction steps. High-speed separations using monolithic columns, staggered separations, parallel separations with multiplexed MS detection, and their combinations have been developed to speed up the separation. To match this increased separation speed, several integrated sample extraction techniques have been developed including on-line high-flow extraction in both a single and a four-way parallel mode, and a fully automated parallel sample preparation platform using a track robot interfaced to a liquid handler. As a result of these integrated separation and extraction techniques, a throughput up to 30 seconds per sample from plasma has been achieved with effective solid phase extraction and high-resolution gradient separation on 10-cm-long columns. The development and applications of these new systems will be presented with an emphasis on the challenges and some of our own unique solutions.
- Bio: Jing-Tao Wu received his Ph.D. in Analytical Chemistry (Mass Spectrometry) from The University of Michigan in 1997 under the direction of Professor David Lubman. In the same year he joined the Drug Metabolism and Pharmacokinetics department of DuPont Pharmaceuticals Company, which recently became part of Bristol-Myers Squibb Company. He is currently a Senior Research Scientist in the Bioanalytical and Structural Chemistry group. Dr. Wu's research interests at DuPont/BMS include high-throughput bioanalytical mass spectrometry, small volume sampling and analyses for microdialysis and intracellular measurements, large-number multiple component assays for cassette dosing, and accurate mass measurement for metabolite identification. He has authored and co-authored 9 publications in these areas in the past two years.
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