Stereoselective separation of (1S, 4S)-sertraline from medicinal reaction mixtures by countercurrent chromatography with hydroxypropyl-β-cyclodextrin as stereoselective selector

Four stereoisomeric components were produced during the synthesis of the antidepressant drug ( 1S, 4S )-sertraline hydrochloride due to the two chiral carbon centers in its chemical structure, including ( 1S, 4S ), ( 1R, 4R ), ( 1S, 4R ), and ( 1R, 4S )-isomer. Stereoselective separation of the target isomer ( 1S, 4S )-sertraline from the medicinal reaction mixtures by countercurrent chromatography using hydroxypropyl-β-cyclodextrin as the stereoselective selector was investigated. A biphasic solvent system composed of n -hexane/0.20 mol/L phosphate buffer solution with pH 7.6 containing 0.10 mol/L of hydroxypropyl-β-cyclodextrin (1:1, v/v) was selected for separation of cis -sertraline and trans -sertraline using reverse phase elution mode and ( 1S, 4S )-sertraline was separated with ( 1R, 4R )-sertraline using recycling elution mode. A fabricated in-house analytical countercurrent chromatographic apparatus was used for optimization of the separation conditions. Stationary phase retention and peak resolution were investigated for separation of cis -sertraline and trans -sertraline by the analytical apparatus.