Metabolite , generally identification

The identification of metabolite structures with LC/MS and LC/MS/MS techniques are an effective approach due to their ability to analyze trace mixtures from complex samples of urine, bile, and plasma. The key to structure identification approaches is based on the fact that metabolites generally retain most of the core structure of the parent drug (Perchalski et al, 1982). Therefore, the parent drug and its corresponding metabolites would be expected to undergo similar fragmentations and to produce mass spectra that indicate major substructures. 

Phase-1 metabolism leads to mass shifts relative to the mass of the parent drag (Table 10.1). In principle, the type of biotransformation can be derived from this mass shift, while more information on the actual site of the modification can be derived from mass shifts of the fragment ions in the MS-MS spectrum. Identification approaches are based on the fact that metabolites generally retain a... 

In standard MS proteomics, well-established and efficient protocols allow for the en masse identification of proteins from tissue extracts. A key step within this process is the initial separation and purification of the molecules before submitting them to the mass spectrometer. However, in MSI studies, a general identification strategy for proteins, peptides, and metabolites is still missing due to several reasons. First, in comparison to LC-MS-based... 

The dividing line between primary and secondary metabolism is somewhat blurred in many cases. For example, amino acids are generally considered to be primary metabolites, but some are sufficiently obscure to be considered as secondary metabolites, whilst sterols which are frequently considered as secondary metabolites are essential to the cell membrane of eucaryotic species, and therefore must be regarded as primary metabolites. Generally, the primary metabolic processes are too similar from group to group to be of much use in identification, but the secondary metabolites which tend to be unique to a small group are used widely. 

The discussion and studies cited previously generally reflect overall tissue distribution of total arsenic after acute exposure in the case of laboratory animals or unknown exposures in the case of humans. Advances in analytical technology in the last decade have facilitated the identification of tissue-specific patterns of metabolite distribution and accumulation in laboratory animals. Kenyon, Del Razo and Hughes (2005a) found that inorganic arsenic was the predominant form of arsenic in the liver and kidney up to two hours post administration of 10 or 100 p mol As kg-1 as inorganic As(V) to female mice, whereas... 

This present chapter will summarise the application of HPLC-NMR and HPLC-NMR-MS to studies of biomedical and pharmaceutical interest and include some limited examples of further hyphenation (hypernation) of UV, NMR, MS and IR spectroscopy that illustrate the potential of these combinations in this field [3,4]. This chapter excludes examples in the drug metabolism field involving the separation, identification, and in some cases, quantification of metabolites in biofluids and their extracts as these are considered elsewhere in this volume. However, because of their general relevance, HPLC-NMR-MS studies of the chemical reactivity of such molecules will be discussed. 

Metabolism data are needed to identify the nature of the terminal residue(s). These studies generally require the use of radiolabeled chemicals. Harvested portions of the crop are analyzed and as many metabolites or alteration products as possible are identified. The tolerance regulation includes identification of the chemical entities covered by the tolerance. 

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