USE OF AMS IN ULTRALOW DOSE HUMAN RADIOACTIVE MASS BALANCE STUDIES

摘要

Metabolism studies using l4C-labelled compounds are an important part of the development of Pharmaceuticals. The 14C-labelled drug is administered to human volunteers and by following radioactivity in blood and excreta, systemic concentrations can be determined along with the routes and rates of excretion. Traditionally, Liquid Scintillation Counting (LSC) has been used to measure radioactivity in samples from such studies. LSC is an insensitive method however as it relies on measuring relatively. infrequent radioactive decay events. Moreover, it is only possible to administer limited amounts of radioactivity to humans, particularly when the compound exhibits a long systemic half-life (t^). In some cases therefore, LSC does not have the required sensitivity to conduct the study. Accelerator Mass Spectrometry on the other hand, measures individual 14C atoms and is a million times more sensitive than LSC. Using AMS, it has been possible to conduct studies on drugs with very ong ti/r In one example, AMS wasused to complete a metabolism study on a drug with a tw of 11 days. Moreover, chromatographic profiles of urine and plasma were obtained using as little as 0.2 dpm of radioactivity.