Dofetilide: tritium labelling by several methods

Despite decades of research, heart disease remains a burden on global health, especially in developed countries. Among problematic cardiovascular indications, abnormal heart rhythms or arrhythmias play a significant role. Dofetilide is a unique cardiovascular drug and one of the earliest antiarrhythmic agents. For many years, compounds labelled with tritium have been extremely useful to facilitate drug discovery research at the receptor level. This paper describes the tritium labelling of dofetilide by several methods. The syntheses and characterization of [phenyl-3H] dofetilide as well as [N-methyl-3H] dofetilide are described in detail. ESI mass spectrometry was found to be an especially useful analytical tool to characterize these valuable radioligands. Because of synthetic efficiency and high specific activity, [N-methyl-3H] dofetilide emerged as the preferred radioligand used by biologists worldwide and information about its storage and stability are also discussed.