title: Analytical and semipreparative chiral separation of cis-itraconazole on cellulose stationary phases by high-performance liquid chromatography.
abstract: cis-Itraconazole is a chiral antifungal drug administered as a racemate. The knowledge of properties of individual cis-itraconazole stereoisomers is vital information for medicine and biosciences as different stereoisomers of cis-itraconazole may possess different affinity to certain biological pathways in the human body. For this purpose, either chiral synthesis of enantiomers or chiral separation of racemate can be used. This paper presents a two-step high-performance liquid chromatography approach for the semipreparative isolation of four stereoisomers (two enantiomeric pairs) of itraconazole using polysaccharide stationary phases and volatile organic mobile phases without additives in isocratic mode. The approach used involves the separation of the racemate into three fractions (i.e. two pure stereoisomers and one mixed fraction containing the remaining two stereoisomers) in the first run and consequent separation of the collected mixed fraction in the second one. For this purpose, combination of cellulose tris-(4-methylbenzoate) and cellulose tris-(3,5-dimehylphenylcarbamate) columns with complementary selectivity for cis-itraconazole provided full separation of all four stereoisomers (with purity of each isomer > 97%). The stereoisomers were collected, their optical rotation determined and their identity confirmed based on the results of a previously published study. Pure separated stereoisomers are subjected to further biological studies.
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Kurka
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic.
authors.forename: Lukáš
authors.initials: L
authors.lastname: Kučera
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Bednář
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification*; D002482:Cellulose / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D017964:Itraconazole / Q000737:chemistry / Q000302:isolation & purification*; D008968:Molecular Conformation; D013237:Stereoisomerism
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole; D002482:Cellulose
keywords: Chiral separation; Itraconazole; Optical rotation detection; Polysaccharide stationary phases; Semipreparative chromatography