tailieunhanh - HPLC for Pharmaceutical Scientists 2007 (Part 13)

Recent advances in mass spectrometry have rendered it an attractive and versatile tool in industrial and academic research laboratories. As a part of this rapid growth, a considerable body of literature has been devoted to the application of mass spectrometry in clinical studies. In concert with separation techniques such as liquid chromatography, mass spectrometry allows the rapid characterization and quantitative determination of a large array of molecules in complex mixtures. Herein, we present an overview of the above techniques accompanied with several examples of the use of liquid chromatography– tandem mass spectrometry in pharmacokinetics/drug metabolism assessment during drug. | 13 THE ROLE OF LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY IN PHARMACOKINETICS AND DRUG METABOLISM Ray Bakhtiar Tapan K. Majumdar and Francis L. S. Tse INTRODUCTION Recent advances in mass spectrometry have rendered it an attractive and versatile tool in industrial and academic research laboratories. As a part of this rapid growth a considerable body of literature has been devoted to the application of mass spectrometry in clinical studies. In concert with separation techniques such as liquid chromatography mass spectrometry allows the rapid characterization and quantitative determination of a large array of molecules in complex mixtures. Herein we present an overview of the above techniques accompanied with several examples of the use of liquid chromatographytandem mass spectrometry in pharmacokinetics drug metabolism assessment during drug development. Since the evolution of pharmaceutical research 1 2 the stages of drug discovery and development have followed three predominant patterns i the systematic and methodical approach by chemists to rationally design and synthesize a molecule to target a specific molecular system . ion channels receptors enzymes DNA ii the isolation and purification of the active ingredients of medicinal plants or microorganisms to screen their spectrum of HPLC for Pharmaceutical Scientists Edited by Yuri Kazakevich and Rosario LoBrutto Copyright 2007 by John Wiley Sons Inc. 605 606 THE ROLE OF LC-MS IN PK AND DRUG METABOLISM activity using in vitro models or iii the serendipitous discovery of a compound with a novel pharmacological action . the accidental discovery of antidepressants . Today one of the increasingly popular and complementary approaches for drug discovery in the pharmaceutical industry is to perform massive parallel synthesis in solution or on a solid support. In addition with the advent of functional genomics and proteomics cell-based assays and molecular biology a multitude of therapeutic targets have been .