Chapter 25 The Use of Isotopically Labeled Compounds in Drug Discovery

Abstract

Publisher Summary The synthesis of radiolabeled compounds can be an integral component of any drug discovery effort from the earliest high-throughput screens to human absorption, distribution, metabolism, and excretion (ADME) and post-marketing studies. Isotopically labeled compounds are critical to the drug development process for being used as radio-ligands in lead discovery, as metabolic tracers in development, and in phase IV clinical studies. This illustrates the uses of long-lived radiolabeled compounds and stable isotope-labeled (SIL) compounds and helps to effectively plan radiochemical syntheses. Radio isotopes are used to improve the sensitivity and ease of the detection of drug molecules in both in vitro and in vivo studies. The low levels of radioactivity in the environment provide a very low background against which the radiolabeled drug can be detected. In addition, the amount of radiation released by the radioactive drug molecule is independent of the structure and accurate quantitation of the parent drug molecule, and its metabolites can be done without the use of reference standards, provided that the radioactive atom is retained in the metabolites.