Enantioseparation of cetirizine by chromatographic methods and discrimination by ¹H‐NMR

Abstract

Cetirizine is an antihistaminic drug used to prevent and treat allergic conditions. It is currently marketed as a racemate. The H1-antagonist activity of cetirizine is primarily due to (R)-levocetirizine. This has led to the introduction of (R)-levocetirizine into clinical practice, and the chiral switching is expected to be more selective and safer. The present work represents three methods for the analysis and chiral discrimination of cetirizine. The first method was based on the enantioseparation of cetirizine on silica gel TLC plates using different chiral selectors as mobile phase additives. The mobile phase enabling successful resolution was acetonitrile-water 17: 3, (v/v) containing 1 mM of chiral selector, namely hydroxypropyl-beta-cyclodextrin, chondroitin sulphate or vancomycin hydrochloride. The second method was a validated high performance liquid chromatography (HPLC), based on stereoselective separation of cetirizine and quantitative determination of its eutomer (R)-levocetirizine on a monolithic C18 column using hydroxypropyl-beta-cyclodextrin as a chiral mobile phase additive. The resolved peaks of (R)-levocetirizine and (S)-dextrocetirizine were confirmed by further mass spectrometry. The third method used a (1)H-NMR technique to characterize cetirizine and (R)-levocetirizine. These methods are selective and accurate, and can be easily applied for chiral discrimination and determination of cetirizine in drug substance and drug product in quality control laboratory. Moreover, chiral purity testing of (R)-levocetirizine can also be monitored by the chromatographic methods.

Chiral separation and quantitation of cetirizine and hydroxyzine by maltodextrin‐mediated CE in human plasma: Effect of zwitterionic property of cetirizine on enantioseparation

“…Also, monolithic silica capillary column modified by coating of cellulose tris(3,5‐dimethylphenylcarbamate) 8 and fused‐silica capillaries packed with silica gel, which was modified by covalent attachment of poly‐ N ‐acryloyl‐l‐phenylalanine ethyl ester 9 as chiral columns, were used for enantioseparation of HZ by CE or nano‐HPLC. Also, there are some reports on the enantioseparation of CTZ by MEKC 12, CE 13–17, NMR spectroscopy 18, HPLC 19–24, subcritical fluid chromatography 25, 26 and mass spectrometry 27 in the literatures. In these methods, clindamycin 12, glycogen 13, amylose 14 and native and derivatized CDs 15–17 were used as chiral selectors for enantioseparation of CTZ.…”