Metabonomics applications

The MAS does not represent a rapid throughput procedure, but because there is no sample extraction or other manipulation prior to analysis, it represents an unbiased method in which changes in tissues can be studied, and as appropriate, compared to alterations observed in biofluids. In this manner, MAS is synergistic with and complimentary to analysis of biofluids by metabonomic applications. Figure 2 shows the typical NMR-MAS spectra from the liver of a control and galactosamine-treated rat. This method readily detects glucose and glycogen, choline and related metabolites and a variety of lipids, and fatty acids. An example of the utility of NMR-MAS data in concert with biofluid analyses is described later in this review. 

Metabonomics has received considerable attention in the toxicological community, but based on published literature, metabonomic applications do not appear to be as widely used as transcriptomics (toxicogenomics). However, this is not a reflection on the utility of the approach, but more likely a consequence of the need to have a complex infrastructure, particularly with respect to data analysis and interpretation in order to carry out the technology. 

With respect to preclinical studies, one interesting observation determined in metabonomic studies, is that vehicles used for compound administration are not biologically inert, and may influence the analysis of metabonomic data. In fact, some commonly used vehicles for compound administration are not compatible with metabonomics applications, most notably Labrofil and polyethylene glycol (21). Finally, because NMR is... 

Shockcor, J.P. and Holmes, E. Metabonomic applications in toxicity screening and disease diagnosis. Curr. Topic Med. Chem. 2002 2 35-51. 

METABONOMIC APPLICATIONS IN TOXICITY SCREENING AND DISEASE DIAGNOSIS... 

Fourier transform ion cyclotron mass spectrometry (FT-ICR-MS) instrumentation offers excellent sensitivity, accuracy (<1 ppm), and high mass resolution (>1,000,000) (Table 10.2). However, because of being too expensive, difficult to use, and not compatible with conventional HPLC columns and flow rates, FTMS has not been frequently used in pharmaceutical research. This changed with an introduction of a hybrid instrument consisting of a linear ion-trap mass spectrometer compatible with LC and an ion-cyclotron-resonance (ICR) detector. Such a hybrid instrument is compatible with conventional HPLC and allows for acquisition of accurate mass data-dependent MS" spectra. Sanders et al. [128] recently reviewed the utility of hybrid LTQ-FTMS for drug metabolism and metabonomics applications while Brown et al. [129] reviewed the metabolomics applications of FT-ICR-MS. 

Although most metabonomics applications have used either NMR spectroscopy or chromatography coupled to mass spectrometry, other techniques have been explored. Fourier transform infrared spectroscopy has been applied to a few metab-olomics investigations including the evaluation of different E. coll mutants by... 

R 548 D. Reichert, Solid-State NMR Spectroscopy and Its Application in Analytical Chemistry , Anal Bioanal Chem., 2003, 376,308 R 549 M. D. Reily, D. G. Robertson, M. Delnomdedieu and J. D. Baker, High Resolution NMR of Biological Fluids Metabonomics Applications in Pharmaceutical Research and Development , Am. Pharm. Rev., 2003, 6,... 

An LC—MS chromatogram is essentially a three-dimensional data set with separate chromatographic, mass-to-charge (m/z) and ion count (intensity) dimensions. The combination of chromatography and mass spectral approaches can take on many incarnations and are dependent on the nature of the metabonomics investigation. Because of the complexity of most metabonomics samples, the final solution is often a compromise between good science and expediency since the ideal analytical conditions for 1000+ metabolome components is an um-ealistic goal. In this section, we will discuss each of these elements separately with an emphasis on biomedical metabonomic applications. 

R417 F.-P. J. Martin, S. Collino and S. Rezzi, H NMR-Based Metabonomic Applications to Decipher Gut Microbial Metabolic Influence on Mammalian Health , Magn. Reson. Chem., 2011, 49(S1), S47. 

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