Dynamic micellar electrokinetic chromatography. Determination of the enantiomerization barriers of oxazepam, temazepam, and lorazepam.

Abstract

The temperature-dependent enantiomerization barriers of oxazepam, temazepam, and lorazepam have been determined between 0 and 30 degrees C by dynamic micellar electrokinetic chromatography (DMEKC) in an aqueous 20 mM borate/phosphate buffer system at pH 8 with 60 mM sodium cholate as chiral surfactant. Interconversion profiles featuring plateau formation and peak broadening were observed and simulated by the new program ChromWin based on the theoretical plate as well as on the stochastic model using the experimental data plateau height, hplateau, peak width at half-height, wh, total retention times, tR, and electroosmotic breakthrough time, t0. Peak form analysis yielded rate constants k and kinetic activation parameters, deltaG double dagger, deltaH double dagger, and deltaS double dagger, of the enantiomerization of oxazepam, temazepam, and lorazepam. At 25 degrees C, the enantiomerization barrier, deltaG double dagger, was determined to be approximately 90 kJ mol-1 and the half-lives, tau, were determined to be approximately 21 min. The new approach allows the fast and precise determination of enantiomerization barriers in a biogenic environment and it mimics physiological conditions, as no organic modifiers or abiotic chiral stationary phases (CSP) are employed.