tailieunhanh - HPLC for Pharmaceutical Scientists 2007 (Part 11)

Great efficiencies have been achieved in the drug discovery process as a result of technological advances in target identification, high-throughput screening, high-throughput organic synthesis, just-in-time in vitro ADME (absorption, distribution, metabolism, and excretion), and early pharmacokinetic screening of drug leads. These advances, spanning target selection all the way through to clinical candidate selection, have placed greater and greater demands on the analytical community to develop robust high-throughput methods. This review highlights the various roles of high-performance liquid chromatography/mass spectrometry (HPLC/MS) in drug discovery and how the field has evolved over the past several years since the introduction of myriad. | 11 THE EXPANDING ROLE OF HPLC IN DRUG DISCOVERY Daniel B. Kassel INTRODUCTION Great efficiencies have been achieved in the drug discovery process as a result of technological advances in target identification high-throughput screening high-throughput organic synthesis just-in-time in vitro ADME absorption distribution metabolism and excretion and early pharmacokinetic screening of drug leads. These advances spanning target selection all the way through to clinical candidate selection have placed greater and greater demands on the analytical community to develop robust high-throughput methods. This review highlights the various roles of high-performance liquid chromatogra-phy mass spectrometry HPLC MS in drug discovery and how the field has evolved over the past several years since the introduction of myriad high-throughput drug discovery technologies. Included are significant developments in HPLC MS to support target selection proteomics biological screening and assay development high-throughput compound analysis and characterization UV- and mass-directed fractionation for unattended automated compound purification and high-throughput in vitro ADME screening. Focus within the pharmaceutical industry has been to increase the likelihood of successfully developing clinical candidates by optimizing the components of the discovery process . spanning target identification chemical HPLC for Pharmaceutical Scientists Edited by Yuri Kazakevich and Rosario LoBrutto Copyright 2007 by John Wiley Sons Inc. 535 536 THE EXPANDING ROLE OF HPLC IN DRUG DISCOVERY design synthesis compound analysis and purification registration biological and ADME screening. By optimizing each step in the iterative discovery process it is expected that the compound attrition rate will be reduced dramatically as compounds advance into preclinical development. Both HPLC and LC MS enjoy important roles throughout the discovery process as will be highlighted in detail in this review. Once .