Stable isotope applications in drug development and the elucidation of mechanisms of drug metabolism

Over the last 50 years, advances in the production of stable isotopes and mass spectrometry instrumentation have fueled elucidation of endogenous biochemical pathways and underpinned quantitative methodology in analytical chemistry, to name but two areas impacted. The topic covering the use of stable isotopes in pharmacological research is very broad, but the scope of the current manuscript is more restricted, and will focus on the application of 2 H, 13 C and 18 O to elucidate mechanisms of drug metabolism since the early 1980s. In keeping with the commemorative nature of this collection of papers, many of the examples are drawn from the work of Dr. Thomas Baillie and his colleagues. In the latter part of this review, we will also consider the development of stable-label forms of drugs that have recently been approved or are under development.