Abstract: A capillary electrophoresis(CE)method was developed for the quantification of levocetirizine dihydrochloride enantiomeric impurities. Sulfobutyl ether-β-cyclodextrin(SBE-β-CD)and hydroxypropyl-β-cyclodextrin(HP-β-CD)were selected as chiral selectors. Parameters including concentration of chiral selectors, pH of buffer solution, concentration of background electrolyte, and voltage applied were optimized by orthogonal experiment design. The optimal condition obtained was a running buffer consisting of 40 mmol/L sodium dihydrogen phosphate, 85 mg/mL chiral selectors at pH 5. 5 and voltage of 20 kV. The LOD and LOQ were 2. 0 μg/mL and 5. 0 μg/mL for isomers of levocetirizine dihydrochloride, respectively. This method could be applied to test the enantiomeric impurities of drug substance and tablets of levocetirizine dihydrochloride. A factorial experiment was exployed to investigate the complex interaction between SBE-β-CD and HP-β-CD in the separation of cetirizine enantiomers. Results indicated that synergistic effect existed between SBE-β-CD and HP-β-CD, which was only reflected in the apparent mobility rather than in the resolution.