RESOLUTION OF ENANTIOMERIC LORAZEPAM AND ITS ACYL AND O-METHYL DERIVATIVES AND RACEMIZATION KINETICS OF LORAZEPAM ENANTIOMERS

Enantiomeric pairs of lorazepam (LZ) and its 3-O-acyl, 1-N-acyl-3-O-acyl, and 3-O-methyl ether derivatives were resolved on high-performance liquid chromatography columns packed with six different chiral stationary phases (CSPs). Resolution was achieved, with several mobile phases of different solvent compositions and with varying chromatograhic resolutions, on at least five of the six CSPs tested. Resolved enantiomers of LZ underwent racemization, whereas enantiomers of 3-O-acyl and 3-O-methyl derivatives were stable. Racemization half-lives of LZ enantiomers were determined by monitoring changes in ellipticity as a function of time. Stability of LZ enantiomers vary substantially depending on the solvents used.