Stable isotopes labelling compounds

The use of stable isotope labeled compounds as internal standards requires MS detection... 

Internal standard (IS), preferably stable-isotope-labeled compound... 

Another application of LC-NMR in natural products chemistry concerns biosynthetic studies employing feeding experiments with stable isotope-labelled compounds. H NMR spectra allow the determination of the amount of isotopic label incorporated into metabolites, e.g. by observing signals that arise from /-couplings of protons to 13C-labelled nuclei [41,42],... 

Stable-isotope-labeled compounds are the most important standard reagents used in most MS-based assays that require accurate quantification. Measurement of metabolites using stable isotopes is commonly referred to as isotope... 

Six proprietary compounds were from Abbott Laboratories (North Chicago, IL, USA). Two stable isotope labeled compounds and additional proprietary compound from Abbott Laboratories were used as the internal standards. HPLC grade... 

In practice, two possibilities exist the use of a stable isotope-labeled molecule or a radiolabeled IS. The most commonly used stable isotope is deuterium, which can be incorporated relatively easily into molecules. 15N, 13C, and 180 are used too, but to a lesser extent. Considerable efforts have been made to increase the availability and range of stable isotope-labeled compounds. In the United States, the National Stable Isotope Resource Center has been established at the Los Alamos Scientific Laboratories to help meet the need for stable isotope-labeled compounds. Funds have been made available for the synthesis of many labeled compounds in sufficient... 

De Ridder, J. J., and Koppens, P. C. (1978). Discrimination between endogenous and exogenous testosterone in human plasma after oral treatment with testosterone undecano-ate, using stable-isotope labeled compounds and mass spectrometric analysis. In Stable Isotopes. Applications in Pharmacology, Toxicology and Clinical Research (T. A. Baillie, ed.), pp. 157-165. Mcmillan, New York. 

The biosynthetic sequence of alkaloid production in M. cordata was also determined by means of HC using both whole plants and root pieces. It is advantageous in the HC study of metabolic sequences in plants to feed small amounts of compounds (2 mg in 5 ml of solution in this experiment) and stable isotopically labeled compounds instead of radioisotopes. 

G.N. Thompson, P.J. Pacy, G.C. Ford, D. Halliday, Practical considerations in the use of stable isotope labelled compounds as tracers in clinical studies, Biomed. Environ. Mass Spectrom., 18 (1989) 321. 

This review is intended to survey those uses of stable isotopes which are of particular importance in medicinal chemistry. These include their use in 1) structure elucidation, 2) studies of drug metabolism, 3) pharmacokinetic analysis and 4) drugs used in therapy. The use of stable isotopes for investigating intermediary metabolism, and their rapidly expanding use in clinical chemistry will not be reviewed since these topics have been covered elsewhere. Synthesis and biosynthesis with stable isotopes have also been previously surveyed >10 and many articles appear in each issue of the Journal of Labelled Compounds and a few have appeared in Biomedical Mass Spectrometry in the past year. In addition, one recent article has appeared on the use of plants to continously produce stable isotope labeled compounds of pharmacological interest. ... 

Table 2. Relative intensity of mass peaks in stable isotope labeled compounds by ESI-TOF-MS...

In summary, after feeding the stable isotope labeled compounds to V. hilgendotfii, LC/ESI-TOF-MS analyses of Cypridina luciferin extracted from the specimens strongly suggested that three amino acids of L-tryptophan, L-arginine and L-isoleucine participate in biosynthesis of Cypridina luciferin (Scheme 1). 

Mutlib, A.E., Application of stable isotope-labeled compounds in metabolism and in metabolism-mediated toxicity studies, Chem. Res. Toxicol., 21(9), 1672, 2008. 

Leacock Street Pomte-Claire, Quebec H9R IHl Canada Fax 514-697-6148 E-mail info cdniso.com Internet site www.cdniso.com custom synthesis of stable-isotope-labeled compounds... 

Since the 1977 review in Annual Reports, the applications of stable-isotope-labeled compounds to biomedical research have increased dramatically. Three international conferences devoted to the use of stable isotopes in the life sciences and one to synthesis and general applications have been held. Review articles have focused on mass spectrome-tric-based analytical methods, on applications of stable isotopes in clinical and pharmacological research, and on more specific studies concerning problems in drug metabolism, pharmacokinetics and synthesis. The present review covers mainly the literature published since 1981 and focuses on recent developments in the use of stable isotopes for investigations of drug metabolism and disposition. 

Quantitative Applications - The use of stable-isotope-labeled compounds as internal standards for the quantitation of drugs and metabolites in biological fluids offers a unique combination of sensitivity and selectivity of detection for pharmacokinetic studies. The principles of the technique have been outlined, and applications up to 1981 have been compiled. Specific aspects of the isotope dilution method, e.g. its utility as a reference technique and associated procedures for handling the data generated from the use of multiple isotope tracers simultaneously, have been discussed. Examples of isotope dilution methods used in clinical psychopharmacology have also been reviewed. ... 

A further strength of the mass spectrometric detector is its ability to distinguish between analytes labelled with stable isotopes, thereby allowing such compounds to be used as convenient internal standards for quantification of a wide variety of biomedical and environmental compounds. Alternatively, stable-isotope-labelled compounds may themselves be selectively detected and measured in connection with metabolic and isotopic enrichment studies. 

STABLE ISOTOPE LABELLED COMPOUNDS AS INTERNAL STANDARDS... 

Discrimination Between Endogenous and Exogenous Testosterone in Human Plasma After Oral Treatment with Testosterone Undecanoate Using Stable-Isotope-Labeling Compounds and Mass Spectrometrie Analysis Stable Isot., Proc. Int. Symp. 1977... 

S. Daniels, R. Espina, K. Kao, H. Yuan, J. Lin, S. Diamond, B. Johnson, J. Rogers, S. Prakash, S. Unger, D. Christ, G. Miwa, L.-S. Gan and A. E. Mutlib, Application of Stable Isotope-Labeled Compounds in Metabolism and in Metabolism-Mediated Toxicity Studies , Chem. Res. Toxicol., 2008,21,1672. 

Stable isotopes are non-radioactive atoms of the same chemical element, which differ only in their number of neutrons [19]. Many elements also have radioactive (non-stable) isotopes. The most commonly used stable isotopes in studies of macronutrient metabolism are (D or deuterium), C, and 0, while Mg, Mg, a, Ca, Ca, Fe, Fe, Zn, and °Zn are the most commonly used stable isotopes for studies of mineral metabolism. The most commonly used radioactive isotopes are and (tritium) [19]. More than 6(X)0 stable isotope-labeled compounds (tracers) are commercially available for use in metabolic studies. Examples for some of these tracers are [1- C] leucine, [1- C, N] leucine, [ring- Hj] phenylalanine, and [6,6]-D2 glucose. It is currently accepted that these compounds have neghgible biological side-effects, which renders them ethically acceptable for use in children [20]. 

The advantages of stable isotope-labeled compounds compared with their radioactive counterparts are manifold. Most importantly, several different stable isotope tracers can be safely administered simultaneously to the same subject without limiting future studies. The plasma volume which is needed for one study to analyze isotope enrichment is small, allowing even pre-term infants to be studied. On average 0.5 ml of plasma is needed for one study. The intramolecular location of one or more label(s) is determined easily, which allows the assessment of metabolic pathways [19]. 

Stable isotope labeled compounds can be obtained by chemical modification of the molecule. Many labeled products can be purchased from commercial suppliers and ordered from the catalog or on special request. Organic compounds of interest for clinical research are labeled with H, C, N, and/or 0 at one or more positions. Multilabeled substrates containing two or three different labels are also available. The choice of the type of label and the position(s) of labeling may be critical for the success of the application for two reasons. First, metabolism of the substrate may lead to loss of label, when the label is in the wrong position. Secondly, unfavorable MS fragmentation may be a cause of loss of... 

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