9. Expanding the Scope of HTMS Methods

  1. Matthew Cooper4 and
  2. Lorenz M. Mayr5
  1. Tom G. Holt1,2,
  2. Jun Wang1,
  3. Xun Chen1,
  4. Bernard K. Choi1,
  5. Neil S. Geoghagen1,
  6. Kristian K. Jensen1,
  7. Maxine Jonas3,
  8. Qi Luo1,
  9. William A. LaMarr3,
  10. Lorraine Malkowitz1,
  11. Can C. Ozbal3,
  12. Yusheng Xiong1,
  13. Claude Dufresne1 and
  14. Ming-Juan Luo1

Published Online: 24 FEB 2011

DOI: 10.1002/9780470979129.ch9

Label-Free Technologies for Drug Discovery

Label-Free Technologies for Drug Discovery

How to Cite

Holt, T. G., Wang, J., Chen, X., Choi, B. K., Geoghagen, N. S., Jensen, K. K., Jonas, M., Luo, Q., LaMarr, W. A., Malkowitz, L., Ozbal, C. C., Xiong, Y., Dufresne, C. and Luo, M.-J. (2011) Expanding the Scope of HTMS Methods, in Label-Free Technologies for Drug Discovery (eds M. Cooper and L. M. Mayr), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9780470979129.ch9

Editor Information

  1. 4

    Institute for Molecular Bioscience, University of Queensland, Australia

  2. 5

    Biology Unit, Protease Platform, Novartis Pharma AG, Basel, Switzerland

Author Information

  1. 1

    FAST (Facility for Automation & Screening Technologies), Merck Research Laboratories, Rahway, NJ, USA

  2. 2

    Department of Chemistry, Rutgers University, Piscataway, NJ, USA

  3. 3

    BioTrove, Inc., Woburn, MA, USA

Publication History

  1. Published Online: 24 FEB 2011
  2. Published Print: 25 FEB 2011

ISBN Information

Print ISBN: 9780470746837

Online ISBN: 9780470979129



  • expanding the scope of HTMS methods;
  • label-free enzyme assay, and mass spectrometric quantification - of product of enzymatic reactions, developed;
  • high throughput mass spectrometry (HTMS);
  • RapidFire, solid phase extraction (SPE) HTMS technology - for rapid MS analysis;
  • HTMS method, expanded to more relevant in vivo assays - drug discovery project naturally evolved to cell-based secondary assays and animal validation stages;
  • liquid chromatography MS (LCMS) quantitation - of cystathionine via derivatization;
  • size exclusion chromatography (SEC) MS - analytical tool, investigating noncovalent binding of small molecules to macromolecules;
  • HTMS using RapidFire - proven methodology for label-free HTS screens;
  • HTMS methods, utilizing LCMS rather than SEC-MS - applicable to cystathionine analysis;
  • future screening, increase in speed - and decrease in sample size, lower per-well cost of analysis


This chapter contains sections titled:

  • Introduction

  • Development of the HTMS Method for Underivatized Cystathionine in Biological Samples Spanning In Vivo Cell Culture, and Ex Vivo Assays

  • Development of a 2D HTMS Method for Plasma-bound Small Molecules

  • Conclusion

  • References