The use of deuterium oxide as a mobile phase in theroutine analysis of pharmaceutical compounds was investigated. The deuterium exchange of labile hydrogenatoms aids in structural confirmation and elucidation ofunknown impurities and degradation products. Althoughdeuterium oxide as a mobile phase does in some caseschange the retention times, the changes in retention timesdo not interfere with the analysis. A study of the high-performance liquid chromatography system shows thatequilibration times for the deuterium-containing mobilephases are similar to equilibration times with changes ofother mobile phases. The use of this technique in theanalysis of pharmaceutical compounds and other smallmolecules is presented.