Rapid Structure Elucidation of Drug Metabolites by Use of Stable Isotopes

Abstract

1. An improved method for identification of the structure of drug metabolites by mass spectrometry is described.

2. By labelling the drug with a stable isotope the metabolites can be easily identified by the isotope distribution of their fragment ions. The isolation procedure can therefore be reduced to a single 2-dimensional thin-layer chromatogram.

3. Metabolism of 4-morpholino-2-piperazino-thieno[3,2-d]pyrimidine (V-K 774), labelled with ¹³C, was studied in the rat by this method. Significant metabolic transformations of both the piperazine and morpholine substituents were demonstrated.