Enantioseparation of ketoconazole and miconazole by capillary electrophoresis and a study on their inclusion interactions with beta-cyclodextrin and derivatives
Document Type
Article
Publication Date
1-1-2021
Abstract
A chiral separation method coupled with capillary electrophoresis (CE) analysis for ketoconazole and miconazole enantiomers using chiral selectors such as beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-CD (HP-beta-CD) was developed in this study, which included the optimisation, validation and application of the method on the antifungal cream samples. The formation of inclusion complex between the hosts (beta-CD and HP-beta-CD) and guests (ketoconazole and miconazole) were compared and analysed using ultraviolet-visible spectrophotometry, nuclear magnetic resonance (NMR) spectroscopy and molecular docking methods. Results from the study showed that in a concentration that ranged between 0.25 and 50 mg L-1, the linear calibration curves of each enantiomer had a high coefficient of regression (R-2 > 0.999), low limit of detection (0.075 mg L-1) and low limit of quantification (0.25 mg L-1). The relative standard deviation (RSD) of the intraday and interday analyses ranged from 0.79% to 8.01% and 3.30% to 11.43%, respectively, while the recoveries ranged from 82.0% to 105.7% (RSD < 7%, n = 3). The most probable structure of the inclusion complexes was proposed based on the findings from the molecular docking studies conducted using the PatchDock server.
Keywords
Antifungal agents, Capillary electrophoresis, Hydroxypropyl, Cyclodextrin, Inclusion complexes, Molecular docking
Divisions
CHEMISTRY
Funders
Fundamental Research Grant Scheme [203/CIPPT/6711557],USM Research Grant [1001/CIPPT/811322],Universiti Sains Malaysia
Publication Title
Chirality
Volume
33
Issue
1
Publisher
Wiley
Publisher Location
111 RIVER ST, HOBOKEN 07030-5774, NJ USA