The importance of radiochemical analysis of biological fluids before and after lyophilization from animals dosed with [3H]-labeled compounds in drug discovery

Abstract

Carbon-14 has been the preferred isotope for ADME studies, primarily because the position and stability of the label could be better assured. However, the need to synthesize radiolabeled compounds in a much more rapid time frame than is routinely possible with carbon-14 has led to a shift in emphasis to tritium labeling. This change has coincided with the development of 3H NMR spectroscopy, which has provided a rapid and reliable method of assessing labeling specificity. Evaluation of the plasma concentration-time profiles of the parent compound and total radioactivity after dosing with 3H-labeled compounds as well as analysis of plasma, urine and bile samples before and after lyophilization are now routine procedures for lead compounds in drug discovery. In early and late stage drug discovery programs, tritiated compounds are often used to determine the metabolism and disposition characteristics of the compound, in addition to establishing early directions for synthetic chemist.