Stereoselective enrichment and determination of citalopram enantiomers by cation-selective exhaustive injection and sweeping coupled with cyclodextrin modified electrokinetic chromatography

Abstract

An highly sensitive, rapid and enantioselective method was developed for the enantioseparation and determination of citalopram enantiomers by cation selective exhaustive injection-sweeping-cyclodextrin modified electrokinetic chromatography (CSEI-sweeping-CDEKC). The optimized conditions were: 50 mM pH 3.0 phosphate solution with 25 mg·mL^-1 S-β-CD used as background buffer, 50 mbar 300 s hydrodynamical injection of 150 mM pH 3.0 NaH₂PO₄ buffer followed with 5 s water plug, 10 kV 600 s electrokinetic sample injection, -20 kV CDEKC run. Under the optimized conditions, the resolution was Rs=8.04, the enrichment factor as up to 2163 folds, the LOD values were: 3.6 ng·mL^-1 for R-citalopram, 4.1 ng·mL^-1 for S-citalopram, and 3 ng·mL^-1 for both enantiomers in plasma samples. This new method showed good precision, repeatability and stability, which had been successfully applied to the impurity inspection of escitalopram oxalate and the stereoselective pharmacokinetic study of citalopram enantiomers.

Keywords: CSEI-sweeping-CDEKC; Citalopram enantiomers; Enantiomer impurity inspection; Enantioseparation; Stereoselective pharmacokinetic study.