1988 Volume 36 Issue 5 Pages 1834-1840
The kinetics of racemization of oxazepam was examined by an high-performance liquid chromatographic (HPLC) method modified for simultaneous determination of each enantiomer of oxazepam and oxazepam acetate by using a chiral stationary phase in order to clarify the factors affecting the racemization rate. The racemization of oxazepam is too fast to allow the isolation of optically active oxazepam. Optically active oxazepam acetate, which was stable enough in configuration to be isolated by HPLC, could be utilized to determine the racemization rate of oxazepam as follows. In the strongly alkaline pH region, the hydrolysis rate of oxazepam acetate was larger than the racemization rate of oxazepam, and more than 93% enantiomeric purity of oxazepam in solution was obtained on hydrolysis of optically active oxazepam acetate at pH 14 and 0°C. The racemization rates of oxazepam were determined over the pH range from 0.5 to 13.5 at a constant ionic strength of 0.5. The dependence of the racemization rates on the pH, ionic strength and dielectric constant of the reaction mixture suggests that the racemization of oxazepam can be ascribed to spontaneous reaction of neutral oxazepam species in the neutral pH region and to hydroxide ion-catalyzed reaction of neutral oxazepam or to spontaneous reaction of dissociated oxazepam species in the basic pH region.