Drug discovery metabolite identification

Recent Developments in Drug Discovery Metabolite Identification.146... 

RECENT DEVELOPMENTS IN DRUG DISCOVERY METABOLITE IDENTIFICATION... 

With the advent of modern LC/MS instrumentation and sophisticated software, metabolic profiling has gradually become a significant tool to support drug discovery. Early identification of active or toxic metabolites and characterization of metabolic liability of a particular structural series will significantly reduce the cycle time of the lead opti-... 

High-Throughput Strategies for Metabolite Identification in Drug Discovery... 

While metabolite identification remains a lower throughput effort in most cases, it is a very important support procedure for new drug discovery. A thorough review of metabolite identification is beyond the scope of this chapter, so I will provide a brief overview and refer the reader to several recent reviews that will provide a more complete picture.176-184 Ma et al.176 reviewed the application of MS for metabolite identification this comprehensive review describes how different types of MS equipment can be used for metabolite identification. 

Besides, High Resolution/Accurate Mass TOF and Q-TOF spectrometers (Figure 4b) allow full detection at low ppb amounts of drugs and their known and unknown metabolites, and they are fully implemented in Life Science applications like Metabolites Identification (MetID), and Drug Discovery. 

Clarke, N., Cox, K., Dunn-Meynell, K., Korfmacher, W., Lin, C. C., White, R. and Cayen, M., Strategies for Semi-Automated Metabolite Identification in Drug Discovery Using LC-MS", American Society for Mass Spectrometry 1999 Conference Abstract, Dallas, TX, USA, 1999. 

Rindgen, D., Cox, K., Clarke, N. and Korfmacher, W., An Integrated Approach to Metabolite Identification for the Drug Discovery Compound SCH 123 using the Triple Quadrupole, Ion Trap and Q-TOF Instruments, American Society for Mass Spectrometry 2000 Conference Abstract, Long Beach, CA, USA, 2000. 

Clarke, N. J. Rindgen, D. Korfmacher, W. A. Cox, K A. Systematic LC/MS metabolite identification in drug discovery. Anal Chem 2001, 73, 430A-439A. 

The marriage of HPLC to mass spectrometry (MS), now developed into a mature instrumentation, continues to greatly impact many of the separation sciences, especially in pharmaceutical analysis where it has been used in new drug discovery [23,24] and in drug metabolite identification [25-27]. HPLC-MS has also made an impact on lipid research, providing a convenient approach to the analysis of phospholipids and fatty acids [28,29]. It has also greatly benefited the field of proteomics [30-34], especially analysis of protein structure and function. 

Castro-Perez JM. Current and future trends in the application of HPLC-MS to metabolite-identification studies. Drug Discovery Today 12, 249-256, 2007. 

Nassar AEF, Bjorge SM, Lee DY. On-line liquid chromatography-accurate radioisotope counting coupled with a radioactivity detector and mass spectrometer for metabolite identification in drug discovery and development. AnaZyft caZ Chemistry 75, 785-790, 2003. 

Zhang, N., Fountain, S. T., Bi, H., and Rossi, D. T. (2000). Quantification and rapid metabolite identification in drug discovery using API time-of-flight LC/MS. Anal. Chem. 72 800-806. 

Rourick, R. A., Jenkins, K. M., Walsh, J. P., Xu, R., Cai, Z., and Kassel, D. B. (2002). Integration of custom LC/MS automated data processing strategies for the rapid assessment of metabolic stability and metabolite identification in drug discovery. In Proceedings of the 50th ASMS Conference on Mass Spectrometry and Allied Topics, Orlando, FL. 

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