Metabolite identification spectrometry applications

Ma, S., Chowdhury, S.K. and Alton, K.B. (2006) Application of Mass Spectrometry for Metabolite Identification. Current Drug Metabolism, 7, 503-523. 

Ma SG, Chowdhury SK, Alton KB. Application of mass spectrometry for metabolite identification. Current Drug Metabolism 7, 503-523, 2006. 

Hop, C. E. C. A. (2004). Applications of quadrupole-time-of-flight mass spectrometry to facilitate metabolite identification. Am. Pharm. Rev. 7 76-79. 

Corcoran, O., Nicholson, J. K., Lenz, E. M., Abou-Shakra, F., Castro-Perez, J., Sage, A. B., and Wilson, I. D. (2000). Directly coupled liquid chromatography with inductively coupled plasma mass spectrometry and orthogonal acceleration time-of-flight mass spectrometry for the identification of drug metabolites in urine Application to diclofenac using chlorine and sulfur detection. Rapid Commun. Mass Spectrom. 14 2377-2384. 

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

Recently, accelerated mass spectrometry (AMS) have been used in mass balance studies in animals and humans (Garner et al., 2002 Mauthe et al., 1998 Rickert et al., 2005). AMS only requires a small amount of radioactivity (nCi) with a normal dose (not considered as a radioactive study in some countries). However, this technique has limited applications in metabolite identification by connecting LC/MS/MS analysis and radioactivity detection. 

Zhang H, Zhang D, Ray K, Zhu M. Mass defect filter technique and its applications to drug metabolite identification by high-resolution mass spectrometry. J Mass Spectrom 2009b 44 999-1016. 

Ma S, Chowdhury S. Application of liquid chromatography/mass spectrometry for metabolite identification. In Drug Metabolism in Drug Design and Development Basic Concepts and Practice, Zhang D, Zhu M, Humphreys WG, Eds. Wiley, Hoboken, NJ, 2007 pp.319-367. 

Mass spectrometric approaches are also very useful for the measurement of stable isotopes in drug metabolism studies. The application of MS to the quantitative measurement of stable isotope has been limited due to the high cost and sophistication of the instruments necessary for stable isotope enrichment studies. Nonetheless, recent improvements in instrument design and performance, as well as computer software for instrument control, data acquisition, and analysis, have increased the sensitivity and reliability of stable isotopic enrichment studies. These new MS instruments, including continuous-flow isotope ratio mass spectrometry (CF-IRMS) and HPLC-chemical reaction interface mass spectrometry (HPLC-CRIMS) are increasingly less expensive, easier to operate, and accessible for mass balance/ metabolite identification studies with stable isotopes. 

An example of the application of these features to separation of some closely-related marine toxins (Vohner 2002) is shown in Figures 3.13 and 3.14. Many examples of the application of monolithic columns to biomedical applications can be cited. For example, it was shown (Dear 2001) that the use of short monolithic silica columns coupled to mass spectrometry dramatically reduced analytical run times for metabolite identification from in vitro samples with no loss in chromatographic performance. Six hydroxylated metabolite isomers were separated in one minute, with resolution and selectivity comparable to conventional analytical chromatography resulting in reduction of analysis time per sample from 30 to 5 minutes. Similar results were reported (Wu 2001 Hsieh 2002) for rapid qualitative and quantitative analyses in drug discovery programs (i.e., not fully validated). 

Groneman, A.F., M.A. Posthumus, L.G.M.T. Tuinstra, and W.A. Traag Identification and Determination of Metabolites in Plant Cell Biotechnology by Gas Chromatography and Gas Chromatography/Mass Spectrometry. Application to Nonpolar Products of Chrysanthemum cinerariaefolium and Tagetes species. Anal. Chim. Acta 163, 43 (1984). 

Zhao, W., Zhang, H., Zhu, M., Warrack, B., Ma, L., Humphreys, W. G., and Sanders, M. (2006). An integrated method for quantification and identification of radiolabeled metabolites Application of chip-based nanoelectrospray and mass defect filter techniques. In Proceedings of the 54th ASMS Conference on Mass Spectrometry and Allied Topics, Seattle, WA. 

B. 1994. The application of electrospray and neutral-loss mass spectrometry to the identification of the metabolites of S12813 in rat liver slices. Rapid Commun. Mass Spectrom., 8,361-365. 

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