Optimization by Factorial Design of a Capillary Electrophoresis Method for the Chiral Resolution and Determination of Zopiclone and Its Synthesis Precursor

Abstract

A rapid, simple and accurate capillary electrophoretic method has been developed for the determination of zopiclone and its synthesis precursor, zopiclone II, by a factorial design. The compounds are separated in a fused silica capillary (48.5 cm length, 40 cm effective length, 50 µm inner diameter) with UV detection at 215 nm. Separation was achieved with a 60.2 mM phosphate buffer containing 20 mM β-cyclodextrin and 1 M of urea, adjusting the pH to 2.0 and using diazepam as an internal standard. The method was validated in accordance with the International Conference on Harmonization guidelines, appropriate linearity and precision being observed for all compounds. The recoveries obtained ranged between 97.6% and 100.7%. This method is sensitive (detection limits ranged between 2.1 and 7.2 mg L−1) and selective to quantify the enantiomers of zopiclone and its synthesis precursor and could be used to evaluate the chiral intermediates and the enantiomeric purity of the final product.