Modeling and optimization of two phase system for recycling high-speed counter-current chromatographic separation of ketoconazole enantiomers

Abstract

An efficient method using recycling high speed counter-current chromatography (HSCCC) with hydroxypropyl-β-cyclodextrin (HP-β-CD) as chiral selector (CS) is developed for the separation of ketoconazole enantiomers. The separation process was performed with a two-phase solvent system composed of n-hexane/acetic acid isobutyl ester/0.1 mol L-1 phosphate buffer solution with pH = 8.5 containing 0.1 mol L-1 HP-β-CD (2:3:5, v/v/v). Important factors that influence the separation efficiency, including organic solvent system, temperature, the pH value of the aqueous phase as well as type and concentration of chiral selector were investigated experimentally. Influence of the pH value and concentration of chiral selector was modeled and the conditions were further optimized by the model. Pure enantiomers with a purity > 99% were obtained by separating 20 mg racemate via HSCCC. The recovery rates ranged from 85% to 89%.

Separation of six compounds including two n‐butyrophenone isomers and two stibene isomers from Rheum tanguticum Maxim by recycling high speed counter‐current chromatography and preparative high‐performance liquid chromatography

“…Aiming to realize a separation among intractable compounds in repeated HSCCC procedures, recycling elution mode has been confirmed to be a practical mean of separating components which have some differences in distribution coefficient [18][19][20][21][22][23][24][25]. While, this methodology takes a long time, but has almost the same solvent consumption and separated volume.…”

“…For isomers with similar polarity and structures, recycling HSCCC has been confirmed to be a practical mean of separating components which have some differences in distribution coefficient. There have been eight reports on separation of isomers by recycling HSCCC in the latest 5 years [18][19][20][21][22][23][24][25]. However, chiral selector was introduced in these reports.…”

Separation of five flavone glycosides including two groups with similar polarities fromDracocephalum tanguticumby a combination of three high‐speed counter‐current chromatography modes

“…Usually, α-values higher than 1.1 are acceptable, which is much looser than that required by normal HSCCC (α>1.5). Recycling HSCCC has been successfully applied to separate compounds with similar polarities [13][14][15][16][17]. Sometimes, the heart-cut mode is often introduced in recycling HSCCC to improve peak resolution [18,19].…”

Preparative enantioseparation of loxoprofen precursor by recycling countercurrent chromatography with hydroxypropyl‐β‐cyclodextrin as a chiral selector

“…These methods could make up its deficiency to some extent when the enantioseparation factor was in the range of 1.2-1.4. In the recent years, recycling elution mode has been successfully applied in enantioseparation by countercurrent chromatography to improve peak resolution [18,[25][26][27]. Though it requires long elution time, it is very easy to conduct the separation with economical solvent-consumption to obtain a complete enantioseparation.…”