title: Heart-cut achiral-chiral LC-LC method development using factorial design: application to the chiral separation of ketoprofen.
abstract: A two-dimensional achiral-chiral LC-LC method in heart-cut mode for ketoprofen and its enantiomeric fraction determination was proposed. A C8column was used in the first dimension, and the chiral column was an α1-acid glycoprotein. The mobile phase of the chiral system was optimized by a factorial design. The effect of temperature on retention and on enantiomeric resolution was studied. Particular attention was paid to mobile phase compatibility for the two columns and to transferring time, using ketoprofen standards. The R-(-) and S-(+)-ketoprofen retention times were 9 and 11 min, respectively; the resolution was higher than 1.1 and enantiomeric fraction close to 0.5. The method was applied to capsules and gels containing ketoprofen. Factorial design was also used to establish the best conditions for gel sample preparation. Recoveries were 84 and 105 % for capsules and gels, respectively. Graphical abstract Two-dimensional chromatogram for KPF and its enantiomers.
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, Complutense University of Madrid, 28040, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Peñín-Ibáñez
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, Complutense University of Madrid, 28040, Madrid, Spain. mjsantos@ucm.es.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Santos-Delgado
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, Complutense University of Madrid, 28040, Madrid, Spain.
authors.forename: Luis María
authors.initials: LM
authors.lastname: Polo-Díez
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification*; D002853:Chromatography, Liquid / Q000379:methods*; D007660:Ketoprofen / Q000302:isolation & purification*; D012015:Reference Standards; D013237:Stereoisomerism; D013696:Temperature
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007660:Ketoprofen
keywords: Enantiomer determination; Ketoprofen; Pharmaceuticals; Two-dimensional LC-LC direct chiral liquid chromatography