title: Enantioseparation of Racemic Flurbiprofen by Aqueous Two-Phase Extraction With Binary Chiral Selectors of L-dioctyl Tartrate and L-tryptophan.
abstract: A novel method for chiral separation of flurbiprofen enantiomers was developed using aqueous two-phase extraction (ATPE) coupled with biphasic recognition chiral extraction (BRCE). An aqueous two-phase system (ATPS) was used as an extracting solvent which was composed of ethanol (35.0% w/w) and ammonium sulfate (18.0% w/w). The chiral selectors in ATPS for BRCE consideration were L-dioctyl tartrate and L-tryptophan, which were screened from amino acids, β-cyclodextrin derivatives, and L-tartrate esters. Factors such as the amounts of L-dioctyl tartrate and L-tryptophan, pH, flurbiprofen concentration, and the operation temperature were investigated in terms of chiral separation of flurbiprofen enantiomers. The optimum conditions were as follows: L-dioctyl tartrate, 80 mg; L-tryptophan, 40 mg; pH, 4.0; flurbiprofen concentration, 0.10 mmol/L; and temperature, 25 °C. The maximum separation factor α for flurbiprofen enantiomers could reach 2.34. The mechanism of chiral separation of flurbiprofen enantiomers is discussed and studied. The results showed that synergistic extraction has been established by L-dioctyl tartrate and L-tryptophan, which enantioselectively recognized R- and S-enantiomers in top and bottom phases, respectively. Compared to conventional liquid-liquid extraction, ATPE coupled with BRCE possessed higher separation efficiency and enantioselectivity without the use of any other organic solvents. The proposed method is a potential and powerful alternative to conventional extraction for separation of various enantiomers.
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, P.R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, P.R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, P.R. China.|Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, UK.
authors.forename: Huajun
authors.initials: H
authors.lastname: Fan
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wan
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, P.R. China.
authors.forename: Xuehao
authors.initials: X
authors.lastname: Wu
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, P.R. China.
authors.forename: Xunyou
authors.initials: X
authors.lastname: Tang
authors.affiliation: Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, UK.
authors.forename: James Z
authors.initials: JZ
authors.lastname: Tang
mesh_terms: D002851:Chromatography, High Pressure Liquid; D005480:Flurbiprofen / Q000737:chemistry* / Q000302:isolation & purification*; D006863:Hydrogen-Ion Concentration; D059625:Liquid-Liquid Extraction / Q000379:methods*; D013237:Stereoisomerism; D013644:Tartrates / Q000737:chemistry*; D014364:Tryptophan / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D013644:Tartrates; D014867:Water; D005480:Flurbiprofen; D014364:Tryptophan
keywords: aqueous two-phase extraction; biphasic recognition chiral extraction; chiral separation; flurbiprofen enantiomers; synergistic extraction