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

• Published in: Journal of liquid chromatography & related technologies Vol. 32; no. 18; pp. 2654 - 2668
• Main Authors: Gomis, Domingo Blanco, Velasco, Cristina Botas, Sánchez, Ignacio Herrero, Álvarez, M. Dolores Gutiérrez
• Format: Journal Article
• Language: English
• Published: Colchester Taylor & Francis Group 09-10-2009; Taylor & Francis
• Subjects: Analysis; Biological and medical sciences; Capillary electrophoresis; Chiral; Cyclodextrin; Experimental design; General pharmacology; Medical sciences; Pharmacology. Drug treatments; Zopiclone; Agonist; Chemical analysis; Separation; Nitrogen heterocycle; Psychotropic; Lactam; Purity control; Organic carbamate; Precursor; Optimization; Pyridine derivatives; Chiral selector; β-Cyclodextrin; Six membered ring; Enantiomer; Bicyclic compound; Tablet; Sedative; Quantitative analysis; Capillary electrophoresis; Gabaergic agonist; Chiral; Oral form; Hypnotic; Zopiclone; Cyclodextrin; Ultraviolet detector; Optical resolution; Experimental design; Quality control; Dosage form; Carboxamide; Optical purity; Inclusion compound; Factorial design; Gabaergic receptor A; Chemometrics
• ISSN: 1082-6076; 1520-572X
• DOI: 10.1080/10826070903245672

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.