Chlorpheniramine is a potent antihistaminic administered as a racemic mixture, while its clinical activity is mainly associated with the S-enantiomer. In this study, a sensitive and rapid on-line preconcentration capillary electrophoresis (CE) method, cation-selective exhaustive injection (CSEI) and sweeping method was established and validated for the analysis of two chlorpheniramine enantiomers. Parameters influencing separation and enhancement efficiency were investigated, including cyclodextrin (CD) types and concentration, background electrolyte pH, type and content of organic modifier, injection time of water plug, injection time and voltage of sample. A zone of 30mM Tris buffer at pH 3.5 without chiral selector was injected into the capillary followed by a 3s water plug, allowing for the analytes to be electrokinetically injected at a voltage of 10kV for 80s. A 30mM Tris buffer at pH 3.5 consisting of 20mM sulfated-β-cyclodextrin (S-β-CD) and 5% methanol was found to be highly efficient for the separation of the two enantiomers. The present method manifested that high sensitivity (0.025μg/mL for the thethe lower limit of quantification), satisfactory accuracy (89.2%-95.0%) and precision (relative standard deviation within 8.4%) were achieved as well as favourable stability. The extraction recoveries of two enantiomers were both above 72.5%. Finally, the developed method was successfully applied to pharmacokinetic study of the two enantiomers in rat plasma after oral administration of racemic chlorpheniramine.
Keywords: Capillary electrophoresis; Cation-selective exhaustive injection; Chlorpheniramine enantiomers; Enantioseparation; Pharmacokinetic study.
Copyright © 2017. Published by Elsevier B.V.