Chapter 32. The Use of Stable Isotopes in Medicinal Chemistry
Annual Reports in Medicinal Chemistry, ISSN: 0065-7743, Vol: 12, Issue: C, Page: 319-330
1977
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Article Description
Stable isotopes are used in a variety of chemical and biomedical applications. This chapter discusses the uses of stable isotopes in structure elucidation, studies of drug metabolism, pharmacokinetic analysis, and drugs used in therapy. Mass spectrometry is used in medicinal chemistry to determine the structure of therapeutic agents and their metabolites. The use of nuclear magnetic resonance (NMR) and infrared spectroscopy (IR) in conjunction with labeling using stable isotopes is important in solving many structural problems that cannot be solved by other methods. Dynamic interactions of the medicinal agents with biological macromolecules, such as plasma proteins, receptors, or metabolizing enzymes indicate another area that can be studied by NMR and IR using drugs specifically labeled with stable isotopes. Stable isotope dilution is a technique that the unlabeled drug is dosed and the labeled substance serves as carrier and internal standard for the measurement of the drug and its metabolites in biological fluids is the most widely used application of stable isotopes. Two general methods utilizing the stable isotope dilution technique used for the quantification of drugs and their metabolites by mass spectrometry (MS) are: (1) twin-ion technique is used to follow the metabolism of chloropromazine and (2) deuterium is used in determining the enzymatic mechanisms of stable isotopes because of the large mass difference between it and hydrogen. The major disadvantages of the use of stable isotopes are the lack of simple and inexpensive instrumentation for detecting the isotopes, and the cost of synthesizing the labeled compounds.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0065774308615717; http://dx.doi.org/10.1016/s0065-7743(08)61571-7; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84985191995&origin=inward; https://linkinghub.elsevier.com/retrieve/pii/S0065774308615717; http://linkinghub.elsevier.com/retrieve/pii/S0065774308615717; http://dx.doi.org/10.1016/s0065-7743%2808%2961571-7; https://dx.doi.org/10.1016/s0065-7743%2808%2961571-7
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