Liquid chromatography-mass Metabolite identification

Nassar, A. E. (2003). Online hydrogen-deuterium exchange and a tandem-quadrupole time-of-flight mass spectrometer coupled with liquid chromatography for metabolite identification in drug metabolism. J. Chromatogr. Sci. 41 398-404. 

Kratzsch C, Peters FT, Kraemer T, Weber AA, Maurer HH. 2003. Screening, library-assisted identification and validated quantification of fifteen neuroleptics and three of their metabolites in plasma by liquid chromatography/ mass spectrometry with atmospheric pressure chemical ionization. J Mass Spectrom 38 283. 

The system relies upon preliminary fractionation of the microbial crude extract by dualmode countercurrent chromatography coupled with photodiode array detection (PDA). The ultraviolet-visible (UV-Vis) spectra and liquid chromatography-mass spectrometry (LC-MS) of biologically active peaks are used for identification. Confirmation of compound identity is accomplished by nuclear magnetic resonance (NMR). Use of an integrated system countercurrent chromatography (CCC) separation, PDA detection, and LC-MS rapidly provided profiles and structural information extremely useful for metabolite identification (dereplication, Figure 14.1). 

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. 

Blum, W., Aichholz, R., Ramstein, P., Kuhnol, J., Bruggen, J., O Reilly, T., andFlorsheimer, A. (2001). In vivo metabolism of epothilone B in tumor-bearing nude mice Identification of three new epothilone B metabolites by capillary high-pressure liquid chromatography/ mass spectrometry/tandem mass spectrometry. Rapid Commun. Mass Spectrom. 15 41-49. 

Beattie, I. G. Blake, T. X 1989. The structural identification of drug metabolites using thermospray liquid chromatography/mass spectrometry. Biomed. Environ. Mass Spectrom., 18, 872-877. 

Petsalo A, Turpeinen M, Tolonen A (2007) Identification of bupropion urinary metabolites by liquid chromatography/mass spectrometry. Rapid Commun Mass Spectrom 21 2547-2554... 

Liquid C h rom atography/M ass Spectrometry. Increased use of liquid chromatography/mass spectrometry (lc/ms) for structural identification and trace analysis has become apparent. Thermospray lc/ms has been used to identify by-products in phenyl isocyanate precolumn derivatization reactions (74). Five compounds resulting from the reaction of phenylisocyanate and the reaction medium were identified two from a reaction between phenyl isocyanate and methanol, two from the reaction between phenyl isocyanate and water, and one from the polymerization of phenyl isocyanate. There were also two reports of derivatization to enhance either the response or structural information from thermospray lc/ms for linoleic acid lipoxygenase metabolites (75) and for cortisol (76). 

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... 

G. J. Dear, R. S. Plumb, B. C. Sweatman, P. S. Parry, A. D. Roberts, J. C. Lindon, J. K. Nicholson, and I. M. Ismail, Use of directly coupled ion-exchange liquid chromatography-mass spectrometry and liquid chromatography-nuclear magnetic resonance spectroscopy as a strategy for polar metabolite identification, J. Chro-... 

Figure 2 The two most frequently used approaches for metabolomics are NMR spectroscopy and mass spectrometry. To maximize the coverage of the metabolome, these techniques can be combined. This figure shows the analysis of the aqueous fraction of a section of heart tissue that uses NMR spectroscopy, gas chromatography mass spectrometry and liquid chromatography mass spectrometry. Although mass spectrometry approaches are inherently more sensitive than NMR spectroscopy, metabolite identification becomes more difficult.

Mutlib AE, Chen H, Nemeth GA, Markwalder JA, Seitz SP, Gan LS, Christ DD. Identification and characterization ofefavirenz metabolites by liquid chromatography/mass spectrometry and high field NMR species differences In the metabolism ofefavirenz. Drug Metab Dispos 1999 27 1319-1333. 

Dear, G.J. Plumb, R.S. Sweatman, B.C. Parry, P.S. Roberts, A.D. Lindon, J.C. Nicholson, J.K. Ismail, I.M. Use of Directly Coupled Ion-exchange Liquid Chromatography-Mass Spectrometry and Liquid Chromatography-Nuclear Magnetic Resonance Spectroscopy as a Strategy for Polar Metabolite Identification, J. Chromatogr. B 748(1), 295-309 (2000). 

Mitamura, K., Nakagawa, T., Shimada, K., Namiki, M., Koh, E., Mizokami, A. and Honma, S. (2002). Identification of dehydroepiandrosterone metabolites formed from human prostate homogenate using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. J. Chromatogr. A, 961, 97-105. 

Lohmann, W. and Karst, U., Generation and identification of reactive metabolites by electrochemistry and immobilized enzymes coupled on-line to liquid chromatography/ mass spectrometry, Anal. Chem., 79(17), 6831, 2007. 

Beresford, A.P. Macrae, P.V. Alker, D. Kobylecki, R.J. Biotransformation of amlodipine. Identification and synthesis of metabolites found in rat, dog and human urine/confirmation of structures by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. Arzneimittelfor-schung, 1989, 39, 201-209... 

Liquid Chromatography-Mass Spectrometry (LC-MS)-Based Identification of Reactive Metabolites Via Trapping Studies... 

APPLICATION OF LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY FOR METABOLITE IDENTIFICATION... 

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