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

Abstract

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/0.20mol/L phosphate buffer solution with pH 7.6 containing 0.10mol/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.