title: Chiral separation of four stereoisomers of ketoconazole drugs using capillary electrophoresis.
abstract: This work aimed to develop a chiral separation method of ketoconazole enantiomers using electrokinetic chromatography. The separation was achieved using heptakis (2, 3, 6-tri-O-methyl)-β-cyclodextrin (TMβCD), a commonly used chiral selector (CS), as it is relatively inexpensive and has a low UV absorbance in addition to an anionic surfactant, sodium dodecyl sulfate (SDS). The influence of TMβCD concentration, phosphate buffer concentration, SDS concentration, buffer pH, and applied voltage were investigated. The optimum conditions for chiral separation of ketoconazole was achieved using 10 mM phosphate buffer at pH 2.5 containing 20 mM TMβCD, 5 mM SDS, and 1.0% (v/v) methanol with an applied voltage of 25 kV at 25 °C with a 5-s injection time (hydrodynamic injection). The four ketoconazole stereoisomers were successfully resolved for the first time within 17 min (total analysis time was 28 min including capillary conditioning). The migration time precision of this method was examined to give repeatability and reproducibility with RSDs ≤5.80% (n =3) and RSDs ≤8.88% (n =9), respectively.
authors.affiliation: Separation Science & Technology Group (SepSTec), Department of Chemistry, Faculty of Science, Sukdai, Johor Bahru, Johor, Malaysia; Nanotechnology Research Alliance, Universiti Teknologi Malaysia, Sukdai, Johor Bahru, Johor, Malaysia; Ibnu Sina Institute for Fundamental Science Studies, Universiti Teknologi Malaysia, Sukdai, Johor Bahru, Johor, Malaysia.
authors.forename: Wan Aini
authors.initials: WA
authors.lastname: Wan Ibrahim
authors.forename: Siti Rosilah
authors.initials: SR
authors.lastname: Arsad
authors.forename: Hasmerya
authors.initials: H
authors.lastname: Maarof
authors.forename: Mohd Marsin
authors.initials: MM
authors.lastname: Sanagi
authors.forename: Hassan Y
authors.initials: HY
authors.lastname: Aboul-Enein
mesh_terms: D019075:Electrophoresis, Capillary / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D007654:Ketoconazole / Q000737:chemistry*; D000432:Methanol / Q000494:pharmacology; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D013237:Stereoisomerism; D013696:Temperature; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D047392:beta-Cyclodextrins; C000609658:heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin; D012967:Sodium Dodecyl Sulfate; D007654:Ketoconazole; D000432:Methanol
keywords: azole drugs; chiral separation; electrokinetic chromatography; heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin; ketoconazole; sodium dodecyl sulfate