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Integrating Automation Into LC/MS For Drug Discovery Bioanalysis

presented by

David T. Rossi
Parke-Davis Pharmaceutical Research

February 02, 2000

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


Background:

David Rossi got his B.S. in Chemistry from Lebanon Valley College in 1979 and then received a Ph.D. in Analytical Chemistry at Purdue in 1984. The next two years were spent working as a Senior Research Chemist at Monsanto, developing trace and major component methods for characterizing bulk pharmaceuticals. His research continued at Adria Laboratories from 1986-1992, after which he joined the Pharmokinetics, Dynamics and Metabolism Department at Parke-Davis Pharmaceutical Research. At present, David is the Associate Director and Research Fellow for Discovery Bioanalytical in that same department, directing a group of 14 scientists in the development, validation and application of nonroutine bioanalytical methods for trace quantitation of drug candidates in biological and in vitro media, in support of drug discovery. Efforts center on separations and mass spectrometry techniques, including LC-MS-MS and automated bioanalytical sample preparation techniques.

Abstract:

A novel, integrated approach for automated sample handling in drug discovery bioanalysis is described. The process includes aspects of animal study design, biological sample collection, sample processing and high throughput API LC/MS operating in a multiple reaction monitoring (MRM) experiment. A semi-automated 96-well liquid-liquid extraction technique for biological-fluid sample-preparation was developed and used in conjunction with the integrated sample handling approach. One plate of samples could be prepared within 1.5 hr, and the resulting 96-well plate of extracts was directly compatible with the LC/MS. Feasibility studies for development of the process included sample collection map generation and information management, sample collection formatting, evaluation of alternative dilution schemes for high concentration samples, choice of biological fluid, and evaluating the capabilities of the two liquid-handling workstations. Numerous comparisons between the new approach and conventional sample handling approaches gave equivalent drug-quantitation results for several example compounds. This new sampling process has approximately doubled the efficiency (as measured by studies assayed per month) of drug discovery bioanalysis in our laboratory.

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