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Caught in a Parallel World: Stretching the Boundaries of High-Throughput Quantitation

presented by

Mark Cole
Senior Scientist, Pfizer Inc.

April 28, 2000

The Scripps Research Institute, W.M. Keck Foundation Amphitheater


Background:

Dr. Cole received his Ph.D. in Analytical Chemistry at Michigan State University in 1990. After teaching at Michigan State University for one year, he joined the Drug Metabolism Department at Pfizer Inc in 1991. Dr. Cole held steadily increasing roles in this department, during which he was primarily responsible for metabolite identification, technology development and mass spectrometry infrastructure support. He received the Pfizer Central Research Achievement award for his pioneering work in developing automated metabolite data collection systems. In 1998, Dr. Cole joined the newly-founded Candidate Enhancement Group to contribute to a team addressing drug metabolism issues related to candidate attrition. Dr. Cole currently leads a group devoted to developing and running the analytical measurements function of high-throughput ADME screens, as well as developing next-generation LC-MS technologies and methodologies for bioanalysis.

Abstract:

The advent of parallel-format high-throughput screens to measure drug-like properties of compounds presents significant challenges to the analytical chemist. HPLC/MS is presently the most common analytical tool for quantitative analysis due to its advantages of specificity, sensitivity and its broad applicability. However, it is inherently a linear technique characterized by serial injection and analysis of individual samples. Parallel-format high-throughput screens produce hundreds of samples simultaneously, presenting a major limitation to LC/MS analysis by quickly overwhelming the analytical capacity. Despite these limitations, the analytical chemist currently does not have a viable alternative in the form of a sensitive, specific and universal parallel technique. We approach this analytical challenge by focussing on the interplay among all components in the analytical process, building modular and multiplexed LC/MS systems, decreasing idle time throughout the analysis, and implementing modest parallelism. The resulting LC/MS systems achieve throughputs of 400 samples/hour and meet our capacity needs for quickly providing drug metabolism data at the rate of compound synthesis.

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