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Integrated Strategies for Drug Discovery Using Mass Spectrometry

ISBN: 978-0-471-46127-2
568 pages
June 2005
Integrated Strategies for Drug Discovery Using Mass Spectrometry (047146127X) cover image


New strategies and techniques for today's fast-paced discovery process
Today, the pressure is on for high-throughput approaches to accelerate the generation, identification, and optimization of molecules with desirable drug properties. As traditional methods of analysis become antiquated, new analytical strategies and techniques are necessary to meet sample throughput requirements and manpower constraints. Among them, mass spectrometry has grown to be a front-line tool throughout drug discovery.
Integrated Strategies for Drug Discovery Using Mass Spectrometry provides a thorough review of current analytical approaches, industry practices, and strategies in drug discovery. The topics represent current industry benchmarks in specific drug discovery activities that deal with proteomics, biomarker discovery, metabonomic approaches for toxicity screening, lead identification, compound libraries, quantitative bioanalytical support, biotransformation, reactive metabolite characterization, lead optimization, pharmaceutical property profiling, sample preparation strategies, and automation.
* Clearly explains how drug discovery and mass spectrometry are interconnected
* Discusses the uses and limitations of various types of mass spectrometry in various aspects of drug discovery
* Prominently features analytical applications that require trace-mixture analysis
* Provides industry applications and real-world examples
* Shares historical background information on various techniques to aid in the understanding of how and why new methods are now being employed to analyze samples
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Table of Contents


List of Contributors.


1. Miniaturized Formats for Efficient Liquid Chromatography Mass Spectrometry-Based Proteomics and Therapeutic Development. (Gary A. Valaskovic and Neil L. Kelleher).

2. Mass-Spectrometry-Based Drug Screening Assays for Early Phases in Drug Discovery. (Marshall M. Siegel).

3. ESI-FTICR as a High Throughput Drug Discovery Platform. (Kristin A. Sannes-Lowery, Lendell L. Cummins, Shuo Chen, Jared J. Drader, and Steven A. Hofstadler).

4. Mass Spectrometry- Based Proteomic Approaches for Disease Diagnosis and Biomarker Discovery. (Thomas P. Conrads, Haleem J. Issaq, Josi S. Blonder, and Timothy D. Veenstra).

5. Metabonomic Applications in Toxicity Screening and Disease Diagnosis. (John P. Shockcor and Elaine Holmes).

6. The Central Role of Mass Spectrometry in Natural Products Discovery. (Jeffrey R. Gilbert, Paul Lewer, Dennis O. Duebelbeis, Andrew W. Carr).

7. Application of Mass Spectrometry to Compound Library Generation, Analysis, and Management. (Xueheng Cheng and Jill Hochlowski).

8. A Combinatorial Process for Drug Discovery. (David S. Wagner, Richard W. Wagner, Frank Schoenen, and H. Mario Geysen).

9. Application of Technological Advances in Biotransformation Studies. (Carmen L. Fernàndez-Metzler, Raju Subramanian and Richard C. King).

10. Applications of Mass Spectrometry for the Characterization of Reactive Metabolites of Drugs in Discovery. (Jim Wang, Jack Wang, Margaret Davis, William DeMaio, JoAnn Scatina, and Rasmy Talaat).

11. Advances in High Throughput Quantitative Drug Discovery Bioanalysis. (Bradley L. Ackermann, Michael J. Berna, and Anthony T. Murphy).

12. New Strategies for the Implementation and Support of Bioanalysis in a Drug Metabolism Environment. (Walter A. Korfmacher).

13. An Integrated LC-MS Strategy for Preclinical Candidate Optimization. (Jonathan L. Josephs and Mark Sanders).

14. New Approaches for Method Development and Purification in Lead Optimization. (Yining Zhao and David J. Semin).

15. High Throughput Metabolic and Physicochemical Property Analysis: Strategies and Tactics for Impact on Drug Discovery Success. (Edward H. Kerns and Li Di).

16. Organ Perfusion and Mass Spectrometry. (C. Gerald Curtis, Ben Chien, David Bar-Or, and Kumar Ramu).

17. Sample Preparation for Drug Discovery Bioanalysis.(David A. Wells).

18. Automation. (John D. Laycock and Thomas Hartmann).


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Author Information

MIKE S. LEE, PHD is President of Milestone Development Services. He is actively involved with consulting, workshops, and symposia to connect industry needs with innovative technologies and solutions. His research interests include the applications of mass spectrometry for the analysis of proteins, natural products, drug metabolites, impurities, and degradants. Recent work has involved the development of automated orthogonal control systems for electrospray ionization. Formerly, Dr. Lee was director of analytical research and development at Bristol-Myers Squibb (BMS) Pharmaceutical Research Institute where he led interdisciplinary teams that contributed to the Food and Drug Administration's approval of Buspar® and Serzone, and the accelerated development and approval of TAXOL. Dr. Lee is a member of the American Society of Mass Spectrometry, American Association of Pharmaceutical Scientists, and the American Chemical Society. In addition, he has authored over forty scientific papers and issued patents.
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"…this textbook is easy-to-read, clearly organized, and well written by established colleagues in the field." (Journal of the American Society of Mass Spectrometry, March 2006)

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