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/0.20 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.

EnantioselectiveLCanalysis and determination of selective serotonin reuptake inhibitors

“…The elution pattern and relative retention time (in min) for sertraline and its isomeric impurities, in the final optimized method, were 1.05 for cis ‐(1 R ,4 R ),1.0 for cis (1 S ,4 S ), 0.89 for trans ‐(1 S ,4 R ) and 0.84 for trans ‐(1 R ,4 S )‐isomer. The chromatographic separation conditions were identical to those reported by Sun et al () except that there was a slight difference in flow rate and nature of the C 18 column. The Zorbax SB C 18 column is chemically stable (at pH < 2, and 90°C), densely covered, sterically protected, with a di ‐isobutyl n ‐octadecylsilane stationary phase with controlled pore size of 80 Å, designed to reduce or eliminate strong adsorption of basic compounds and give longer column life, and is compatible with water and all common organic solvents.…”

“…Sun et al () used HP‐ β ‐CD in the CMPA approach to analyze the trans ‐crude product and cis ‐crude product [obtained from the reaction mixture of the synthesis of the drug (1 S ,4 S )‐sertraline hydrochloride carried out in their laboratory] by RPHPLC using the following chromatographic conditions: column, YMC‐Pack ODS‐A ( l × i.d., 150 × 4.6 mm, 5 μm particle size); mobile phase, acetonitrile–0.17 mol L −1 of phosphate buffer pH 3.0 containing 20 mmol L −1 of HP‐ β ‐CD (25:75, v/v) at a flow rate of 0.85 ml min −1 ; and detection wavelength, 225 nm (Figure ). Both trans ‐crude product and cis ‐crude product contained four isomers, i.e.…”

“…RPHPLC separation of the synthesized trans ‐crude product (a), and cis ‐crude product (b) [obtained from the reaction mixture of the synthesis of the drug (1 S ,4 S )‐sertraline hydrochloride], using column, YMC‐Pack ODS‐A (150 × 4.6 mm, 5 μm particle size); mobile phase, acetonitrile–0.17 mol L −1 of phosphate buffer pH 3.0 containing 20 mmol L −1 of HP‐ β ‐CD (25:75, v/v) at a flow rate of 0.85 ml min −1 ; detection wavelength, 225 nm; column temperature, 25°C (reproduced from Sun et al, , with permission, © John Wiley and Sons) . …”

Enantioseparation of ondansetron by countercurrent chromatography using sulfobutyl ether‐β‐cyclodextrin as chiral selector

“…Substituted β‐cyclodextrin is one of the most conspicuous and developmental potential chiral selectors due to its special stereoscopic structure and properties [27]. Hydroxypropyl‐β‐cyclodextrin, as the most widely used neutral β‐cyclodextrin, plays an important role in chiral countercurrent chromatography [20,22,23,28–33]. Limited number of literatures reported other substituted β‐cyclodextrins such as hydroxyethyl‐β‐cyclodextrin [21], carboxymethyl‐β‐cyclodextrin [24,34,35], sulfated‐β‐cyclodextrin [36,37], and methyl‐​β‐​cyclodextrin [38].…”

Application of accelerated solvent extraction coupled with online two‐dimensional countercurrent chromatography for continuous extraction and separation of bioactive compounds from Citrus limon peel

“…ASE is advantageous over many conventional extraction techniques due to its high extraction yield, large capacity, and increased extraction efficiency [10]. CCC is a unique liquid-liquid partition chromatography technique without a solid support, which circumvents the adsorption of bioactive compounds to a solid stationary phase, artifact formation, tailing of solute peaks, and any possible contamination [11]. An online combined technology of ASE and CCC was established [12,13] for the extraction and online separation of chemical constituents.…”