Resolution of ketoconazole enantiomers by high-performance liquid chromatography and inclusion complex formation between selector and enantiomers

Abstract

The analytical resolution of ketoconazole (KTZ) enantiomers was performed by high-performance liquid chromatography with sulphobutylether-β-cyclodextrin (SBE-β-CD) as a chiral mobile phase additive (chiral selector). Some important factors affecting the resolution of KTZ enantiomers were investigated. In addition, the molecular interaction between KTZ and SBE-β-CD was studied using the UV absorption spectrum and HPLC for an understanding of the resolution process. The results show that the type and concentration of the chiral mobile phase additive, the pH of the mobile phase and the volume fraction of methanol (φMeOH) in the mobile phase all have a clear influence on the resolution of KTZ enantiomers. Under optimal conditions, namely the use of 0.5 mmol L −1 SBE-β-CD as the chiral mobile phase additive, pH of 4.0 and φMeOH in the mobile phase of 0.6, KTZ enantiomers are resolved with a resolution of 3.74. SBE-β-CD can bind to KTZ with a stability constant of 1157. The chromatographic method can provide the complexation stability constants of (+)-KTZ with SBE-β-CD (K (+) ) and (-)-KTZ with SBE-β-CD (K (−) ). The intrinsic enantioselectivity was calculated from the K (+) to K (−) ratio as 1.34.

Enantioseparation of basic drugs by reverse phase high‐performance liquid chromatography system using carboxymethyl‐β‐cyclodextrin as chiral mobile phase additive

“…11,12 On the other hand, the method of utilizing the CMPA has been widely used in exploratory research as a versatile and flexible method to demonstrate greater potential in chiral separation. 13,14 So far, a wide range of chiral selectors, including cyclodextrins (CDs), [14][15][16][17][18] chiral ion-pair inclusions, 19,20 and chiral ligand-exchange inclusions, [21][22][23] have been explored in CMPA techniques.…”

Enantioseparation of ondansetron by countercurrent chromatography using sulfobutyl ether‐β‐cyclodextrin as chiral selector

“…Limited number of literatures reported other substituted β‐cyclodextrins such as hydroxyethyl‐β‐cyclodextrin [21], carboxymethyl‐β‐cyclodextrin [24,34,35], sulfated‐β‐cyclodextrin [36,37], and methyl‐​β‐​cyclodextrin [38]. Sulfobutyl ether‐β‐cyclodextrin showed impressive high enantiorecognition in the separation of N‐alkyl alkaline compounds as an anionic β‐cyclodextrin in traditional chiral liquid chromatography [39–42] and chiral capillary electrophoresis [43–46]. However, only three papers have been published so far with regard to enantioseparation by countercurrent chromatography using sulfobutyl ether‐β‐cyclodextrin as chiral selector [19,47,48], and only one literature reporting its use in enantioseparation of alkaline racemate by countercurrent chromatography [47].…”