Metabolic profiling metabolite identification

Figure 3.4 GC/MS metabolic profile of a polar M. truncatula root extract that provides the identification for many of the root components. Individual components are identified by matching their mass spectra to those in databases or by comparison with authentic samples. Using this approach we have identified a large number (>130 currently) of primary metabolites in M. truncatula.

With the advent of modern LC/MS instrumentation and sophisticated software, metabolic profiling has gradually become a significant tool to support drug discovery. Early identification of active or toxic metabolites and characterization of metabolic liability of a particular structural series will significantly reduce the cycle time of the lead opti-... 

The urine is collected according to the preinstructed collection intervals directly from the urine collection container of the metabolism cage. The samples are weight and directly after stirring and homogenizing the urine, aliquots are taken for radioanalysis. The remainder is bottled and frozen for additional investigations planned (metabolite profile and identification and/or bioanalysis). 

While metabolite identification studies provide critical information on drug candidates, these studies have typically been reserved for compounds late in the development phase. These studies are not amenable to high throughput as each compound will give a different metabolic profile, and evaluation of the data can be a lengthy and labor-intensive process. Traditional studies required radio labeled compounds,... 

NMR spectroscopy is in many respects an ideal analytical technology for metabolic profiling because it is equally sensitive to all metabolites, it can provide quantitative results, direct analysis, metabolite identification, and broad metabolite class coverage. However, NMR spectroscopy gives information only for the abundant metabolites (due to the method s relatively poor... 

JI Usansky, LA Damani. The urinary metabolic profile of metyrapone in the rat. Identification of two novel isomeric metyrapone N-oxide metabolites. Drug Metab Dispos 20 64, 1992. 

The variations in human metabolic profiles can seldom permit visual observations of meaningful metabolic deviations from the normal. However, large computer systems do have the general capability to extract the distinct features from large data sets, and reduce the bulk of data from capillary GC of numerous patients to a more easily understandable form. Precisely measured retention characteristics and the peak areas form the basis for such comparisons. Pattern recognition methods have been utilized to classify diabetic samples [169,170] and those of virus-infected patients [171] with the aid of training sets from clinically defined cases. In addition, the feature extraction approach [169,170] permits identification of important metabolite peaks in complex chromatograms. 

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