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The Use of Stable Isotopes in Medicinal Chemistry

Identification of metabolites - Stable isotopes as tracers Stable isotope labeiled compounds as internal standards Studies of bioavailability [Pg.2]

Total body water - Variation with age Body water changes during pregnancy Body composition and energy balance Intercompartmental water movement Biochemical investigations Carbon-13 [Pg.2]

Breath tests Glucose metabolism Miscellaneous Nitrogen-15 [Pg.2]

Urea and ammonia Creatine-creatinine Uric acid [Pg.2]

The intention in this review is to illustrate the use of stable isotopes in fields of interest to the medicinal chemist. Selection is inevitable. It is therefore proposed to outline the more important methods used for the separation of the isotopes and to describe some of the problems that confront the synthetic chemist in the preparation of labelled compounds. Of the wide variety of applications, the potential in clinical work has as yet been barely realised and it is therefore opportune to pay particular attention to such uses. The isotope mass spectrometer is of especial importance in such studies and this technique will be treated in some detail. [Pg.2]

AVAILABILITY OF STABLE ISOTOPES Separation of stable isotopes Carbon isotopes Nitrogen isotopes Oxygen isotopes Sulphur isotopes Synthesis of labelled compounds [Pg.1]

The isotope mass spectrometer The gas inlet system The ion source The ion collectors Measurement of the isotope ratio Expression of enrichment Analytical accuracy [Pg.1]

Gas chromatography-mass spectrometry (SIM) Sample preparation for isotopic analysis Deuterium Carbon-13 Nitrogen-15 Oxygen-18 Sulphur-34 [Pg.1]

Nuclear magnetic resonance spectroscopy Optical emission spectroscopy Infrared spectroscopy Miscellaneous methods [Pg.1]


SD Nelson, LR Pohl. The use of stable isotopes in medicinal chemistry. In Annual Reports in Medicinal Chemistry. Vol. 12. New York Academic Press, 1977, pp 319-329. [Pg.348]

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. ... [Pg.319]

II. Use of Stable Isotopes for Structure Elucidation - Mass spectrometry is commonly used in medicinal chemistry to determine the structure of therapeutic agents and their metabolites. The unequivocal interpretation of the mass spectrum for most classes of compounds requires the use of derivatives which are labeled specifically with stable isotopes. For example, the loss of 16 mass units from hydroxamic acids was shown to be due to the loss of the hydroxylamino oxygen by specific labeling with... [Pg.319]

Compounds labeled with isotopes have played an important role in chemistry, biology, and medicine since they were first used as tracers by Hevesey. - Both stable - and radioactive isotopes were utilized in early investigations, but the situation changed dramatically with the invention of the cyclotron by Lawrence in 1930 and the construction of the nuclear reactor by Fermi in 1942 that enabled access to radioisotopes on a regular basis. Radioisotope use in medicine was also accelerated by advances in radiation-detection techniques. The development of single-photon emission computerized tomography (SPECT) " and positron emission tomography revolutionized... [Pg.91]


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