Metabolite identification significance

The significant differences observed in the positive and negative ion mass spectra of fluorinated pyridines greatly assist metabolite identification in biological... 

Tlie distribution is so diffuse that little if any information can be obtained to indicate a metabolic pathway or provide a mechanism of metabolic transformation. Our experience in using this approach has resulted in a considerable amount of time in extraction and purification without a significant amount of metabolite identification beyond organosoluble metabolites. The results are useless in supporting toxicity studies. Perhaps the metabolism studies are too limited in their design and should be expanded to support toxicity studies. 

The availability of the chemical structure and NMR assignment s for the parent compound, as illustrated in Section 12.7 for Buspirone, significantly simplifies the identification of related metabolites. A significant amount of information has already been accumulated and presented in the literature that describes numerous metabolic reactions associated with a variety of metabolic pathways. Examples of the most common metabolic reactions are tabulated in Table 12.11. These metabolic reactions identify a range of possible chemical modifications that may be applied to the parent compound and generate a variety of related metabolites. 

With modern QTOF and Orbitrap mass spectrometers, mass resolution of 10" 10 with a mass accuracy within 5 ppm is routinely achieved. The advances in HRMS have not only provided accurate MS measurement but also signifieantly improved the specificity of LC—MS-based metabolite identification approaches in recent years (Tiller et al., 2008 Zhang et al., 2008a). For example, specificity of background subtraction in high-resolution full scanning is significantly improved. Current HRMS measures m/z values with precision at... 

The purist s approach to data-up metabolite identification might be to evaluate each analyte-specific peak in turn, determining the biotransformation from the accurate m/z obtained for the metabolite, in practice, a significant proportion of metabolites—those formed on the basis of classical phase 1 or phase 2 biotransformations can be retrieved on the basis of narrow-window extracted... 

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