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API LC-MS/MS Applications in Pharmacology & Toxicology Research

presented by

Kanyin E. Zhang
Agouron Pharmaceuticals, Inc.

March 25, 1997

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


Background:

Dr. Kanyin Zhang received his B.S. degree in Chemistry from the Beijing University in China in 1984, and an M.S. degree also in Chemistry from the University of Minnesota in 1986. He then pursued his graduate career in Medicinal Chemistry with Dr. Tom Baillie at the University of Washington in Seattle, where he studied drug metabolism using mass spectrometry. After completing his Ph.D. in 1992, he went to Merck Research Laboratories in West Point, PA as a Senior Research Chemist in Drug Metabolism. Last year, Kanyin moved back to the west coast to join Agouron where he currently holds a position as a Senior Research Chemist in Development Pharmacology. His group at Agouron uses LC-MS/MS as a primary tool to support drug metabolism as well as some bioanalytical needs in drug discovery and development.

Abstract:

Mass spectrometry has long been an integral part of pharmacological and toxicological research because it provides the sensitivity and structural information that no other technique can offer. Moreover, its value has increased since the invention of atmospheric pressure ionization (API), electrospray in particular, LC-MS interface. Drug molecules and their metabolites that previously could not be ionized and quantified by GC-MS, thermospray/ particle beam LC-MS or FAB-MS suddenly became visible to API LC-MS on a routine basis. The enormous ability of API coupled with tandem mass spectrometry provides not only structural information for drug metabolites, but also the selectivity and sensitivity required to detect low levels of analyte(s) from complex biological matrices. As a result, the use of API LC-MS/MS drug analysis in pharmacokinetic studies has emerged as a nearly universal and high throughput method to support drug discovery and development. API LC-MS/MS has made an equally significant impact in the field of drug metabolism. Important questions, such as those concerning the formation of active or toxic metabolite(s) can be addressed much more quickly by LC-MS/MS than by conventional off-line techniques. Kanyin's presentation at the upcoming SANDMAN meeting will outline these applications and illustrate with examples.

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