Abstract Multi-deuterium incorporations into drugs, such as theophylline, caffeine, valpromide, phenytoin, and trimethoprim, were post-synthetically achieved by Pd/C-, Pt/C-, or/and Rh/C-catalyzed hydrogen–deuterium exchange reactions under neutral conditions using deuterium oxide as the deuterium source in the presence of hydrogen gas. The present study offers facile and convenient methods for the preparation of highly ...