Drug metabolites identification using

Dear GJ, Plumb RS, Sweatman BC et al. (2000) Mass directed peak selection, an efficient method of drug metabolite identification using directly coupled liquid chromatography-mass spectrometry-nuclear magnetic resonance spectroscopy. J Chromatogr B Biomed Sci Appl 748 281-293... 

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. 

Metabolite identification using LC-MS techniques is based on the fact that metabolites generally retain most of the core structure of the parent drug [56,87,88], Therefore, the parent drug and the corresponding metabolites would be expected to undergo similar fragmentations and produce mass spectra that indicate major substructures. 

In a recent report, Tiller et al. [45] described increased throughput for drug metabolite identification studies in the early discovery phase with a record of 21 diverse structural classes of NCEs assayed in one day using AM LC-MS/MS on a Waters QTOF Premier MS system (Waters, Milford, MA, United States) and targeted data analysis procedures. An MSE experiment [46], utilizing dynamic range enhancement... 

The Use of Target-Compound Analysis and LC-MS-MS for the Identification of Drug Metabolites... 

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. 

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. 

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