Hydrogen-deuterium (H-D) exchange reaction of warfarin in D2O solution

Abstract

To prove the presence of a hydrogen-deuterium (H-D) exchange reaction, 1H- and 13C-NMR spectra of warfarin were measured in solvents containing D2O and H2O. In D2O or D2O/dimethyl sulfoxide (DMSO)-d6 solvent, signal pattern changes were observed on H12 and H11 as well as 14 methyl protons over time while no changes were observed on H2O or H2O/DMSO-d 6 solvent. The observed changes in the solvents containing D 2O were concluded to be caused by the H-D exchange reaction on H12, the process of CH2→CHD→CD2. MS spectroscopy also confirmed these H-D exchanges. The kinetics of this reaction were analyzed as the successive reaction, and the mechanism was also proposed. © 2009 Pharmaceutical Society of Japan.