[Separation of ketoconazole enantiomers using high performance liquid chromatography with chiral mobile phase additives]

Abstract

A simple and effective method for the separation of ketoconazole enantiomers was developed using the chiral mobile phase additive on a C18 reversed-phase column. Several beta-cyclodextrins were investigated as chiral mobile phase additives separately. The results showed that ketoconazole enantiomers were well separated by only adding sulfobutyl ether-beta-cyclodextrin (SBE-beta-CD) into the mobile phase. Excellent enantioseparation was achieved with the mobile phase composed of methanol-0.02 mol/L NaH2PO4 (60:40, v/v, containing 1.0 mmol/L SBE-beta-CD and 0.02% triethylamine, at pH 3.00 adjusted with phosphoric acid aqueous solution). The flow rate was 1.0 mL/min. The detection wavelength was set at 225 nm and the column temperature at 30 degrees C. Under the optimized conditions, the resolution of ketoconazole enantiomers was 2.05.