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Radiolabeling/radiolabeled metabolite identification

Reviews on the fate of aromatic hydrocarbons in marine organisms have been published (2,3,4). They indicated that a substantial amount of information exists on the accumulation of these compounds in a variety of phylogenetically diverse organisms. Recently, emphasis has shifted toward studies of bioconversions of these hydrocarbons. Work has been conducted on enzymes mediating the degradation of aromatic hydrocarbons and on the formation and retention of metabolites. Identifications of individual metabolites in tissues and body fluids of several marine organisms exposed to radiolabeled aromatic hydrocarbons have been made however, insufficient information is available to determine the extent of differences in metabolite profiles as evinced from chromatographic data. [Pg.57]

Isotopic cluster analysis can be built into the automated processing method and is used to target potential metabolites with the desired isotope ratios (Kind and Fiehn, 2006). For example, chlorine or bromine or radiolabeled drugs/metabolites can be pinpointed, at low levels, within a complex matrix background to dramatically enhance specificity and increase confidence in metabolite identification (Jindal and Lutz, 1986 Shirley et al., 1997). [Pg.172]

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. [Pg.251]

Zhu, M., Zhang, D., and Skiles, G. L. (2005). Quantification and structural elucidation of low quantities of radiolabeled metabolites using microplate scintillation counting techniques in conjunction with LC-MS. In Identification and Quantification of Drugs, Metabolites and Metabolizing Enzymes by LC-MS (Chowdhury, S. K., Ed.). Elsevier, Amsterdam, pp. 195-223. [Pg.273]

In vitro studies can only give a limited, mechanistic picture of biotransformation in animals or humans. The quantitative importance of each individual metabolite can only be assessed in vivo. Also, samples collected from in vivo studies give rise to comprehensive metabolite identification work (Watt et al. 2003 Clarke et al. 2001) which is also required from a regulatory point of view (Baillie et al. 2002). Due to the labour-intense nature of these studies and the need of applying radiolabeled compounds in order to get a complete picture of biotransformation these studies are performed at a later stage of development during preclinical and clinical phase. [Pg.500]

As the compound reaches the late discovery and candidate selection stage, the focus is to determine its major metabolic pathways, metabolic difference between species, and to identify potential pharmacologically active or toxic metabolites. Because of the complexity, comprehensive metabolite characterization studies have been typically conducted at this stage with radiolabeled standard. Identification of circulating metabolites is also important at this stage to explain the pharmacokinetic or the pharmacodynamic profile. An NCE may show efficacy that is inconsistent with what is predicted based upon the known concentration of the parent drug. These inconsistencies could be due to the presence of active metabolites. The knowledge of these metabolites will also dictate how the analysis of samples will be conducted in the development and clinical studies. [Pg.231]

The use of radiolabeled drugs is not only crucial for the quantification of unknown metabolites but has also long played a critical role in metabolite identification studies. The utility of radiolabeled substrates inelude (1) their use as tracers of drug-related components during sample elean-up, eoneentra-tion, profiling, and isolation from complex biological matrixes and (2) facilitation of LC-MS/MS detection of radiolabeled metabolites based on their HPLC retention times, peak shapes, and in some cases, isotopic ratios. [Pg.302]

FIGURE 10.8 A set up of integrated approach using a combination of RFD, MSC, and mass spectrometers for quantification and identification of both high and low levels of radiolabeled metabolites. [Pg.305]

Hyphenation of HPLC with NMR combines the power of sepai ation with a maximum of stiaictural information by NMR. HPLC-NMR has been used in the detection and identification of diaig metabolites in human urine since 1992. The rapid and unambiguous determination of the major metabolites of diaigs without any pretreatment of the investigated fluid represents the main advantage of this approach. Moreover the method is non-destmctive and without the need to use radiolabelled compounds. [Pg.342]

Of particular interest in brevetoxin research are the diagnosis of intoxication and identification of brevetoxins and their metabolites in biological fluids. We are investigating the distribution and fate of radiolabeled PbTx-3 in rats. Three model systems were used to study the toxicokinetics and metabolism of PbTx-3 1) rats injected intravenously with a bolus dose of toxin, 2) isolated rat livers perfused with toxin, and 3) isolated rat hepatocytes exposed to the toxin in vitro. [Pg.178]

Validation of true extraction efficiency normally requires the identification and quantitation of field-applied radiolabeled analyte(s), including resulting metabolites and all other degradation products. The manufacturer of a new pesticide has to perform such experiments and is able to determine the extraction efficiency of aged residues. Without any identification of residue components the calculation of the ratio between extracted radioactivity and total radioactivity inside the sample before extraction gives a first impression of the extraction efficiency of solvents. At best, this ratio is nearly 1 (i.e., a traceability of about 100%) and no further information is required. Such an efficient extraction solvent may serve as a reference solvent for any comparison with other extraction procedures. [Pg.110]

Identification and pharmacokinetics of major metabolites, often using radiolabelled drug... [Pg.195]

In many instances, such as in studies of metabolism or degradation where the sensitivity is not so important, TLC and radioscanning provide a quick and simple technique for the identification and quantitation of radiolabeled metabolic products. An example of a radiochromatogram scan is shown in Fig. 2.13 for the analysis of some metabolites of the insecticide ethyl parathion in a microsomal enzyme preparation from rat liver [SI]. [Pg.34]

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. [Pg.11]

This paper is the only one in the liquid chromatography portion of this symposium which will attempt to deal with chromatography specifically from the viewpoint of the pesticide metabolism chemist. A residue analyst knows what compound he must analyze for, and develops his method with the properties of that substance in mind. On the other hand, the pesticide metabolism chemist has a different problem. At the conclusion of the treatment, exposure, and harvest phases of a radiolabeled metabolism study, he divides his material into appropriate samples, and extracts each sample with selected solvents to obtain the radioactive materials in soluble form. Typically these extracts consist of low levels (ppm) of carbon-14 labeled metabolites in a complicated mixture of normal natural products from the plant, animal, or soil source. The identity of each metabolite is unknown, and each must be isolated from the natural background and from other labeled metabolites in sufficient quantity and in adequate purity for identification studies, usually by mass spectrometry. The situation is rather like looking for the proverbial "needle in the haystack" when one does not know the size, shape,or composition of the needle, or even how many needles there are in the stack. At this point a separation technique must be selected with certain important requirements in mind. [Pg.1]

Other detection principles have been applied to HPLC, e.g. conductivity, radioactivity, infra-red, and photoconductivity detectors. Such detectors are not widely used in drug analysis but can find application in special circumstances (e.g. the identification of drug metabolites arising from a radiolabelled drug by radioactivity detection). [Pg.204]


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See also in sourсe #XX -- [ Pg.310 ]




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Metabolite identification

Radiolabeling

Radiolabeling/radiolabeled

Radiolabelling

Radiolabels

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