Metabolite identification liquid chromatography-accurate

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. 

Gu, M., Wang, Y., Zhao, X. G., and Gu, Z. M. (2006). Accurate mass filtering of ion chromatograms for metabolite identification using a unit mass resolution liquid chromatography/ mass spectrometry system. Rapid Commun. Mass Spectrom. 20 764-770. 

Tiller, P. R., Yu, S., Castro-Perez, J., Fillgrove, K. L., and Baillie, T. A. (2008). High-throughput, accurate mass liquid chromatography/tandem mass spectrometry on a quadrupole time-of-flight system as a first-line approach for metabolite identification studies. Rapid Commun. Mass Spectrom. 22 1053-1061. 

Superior sensitivity, efficiency, and specificity have made high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), the predominant analytical technique for characterization and quantitative analysis of metabolites (Kostiainen et al., 2003 Ma et al., 2006 Prakash et al., 2007). Ion trap, triple-quadrupole, and quadmpole time-of-flight (Q-TOF) mass spectrometers are routinely used to profile and characterize metabolites in plasma and excreta (Ma et al., 2006). The combination of scan types and features available on mass spectrometers of different design (product ion, MS", neutral loss, precursor ion scans, accurate mass measurements) allows identification and characterization of putative and unexpected metabolites with or without little prior knowledge of biotransformation pathways of a given dmg molecule. 

Liquid chromatography—mass spectroscopy has become one of the most powerful analytical techniques in the drug discovery and development proeess. LC tandem MS is obviously the technique of choice for the identification of metabolites as illustrated in this chapter. Exact mass measurements and elemental composition assignment are essential for the characterization of the metabolites. Accurate mass measurements of the product ions, formed in an MS/MS experiment, greatly facilitate the structure elucidation of the metabolites. With the ever evolving technological advances in mass spectrometry and separation science, LC MS will continue to play an important role in metabolite identification in the future. 

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