Enantioseparation of ketoconazole and miconazole by capillary electrophoresis and a study on their inclusion interactions with β‐cyclodextrin and derivatives

• Published in: Chirality (New York, N.Y.) Vol. 33; no. 1; pp. 37 - 50
• Main Authors: Azhari, Nurul Raihana, Yahaya, Noorfatimah, Mohd Suah, Faiz Bukhari M., Prabu, Samikannu, Yih Hui, Boon, Shahriman, Mohamad Shariff, Mohamad Zain, Nur Nadhirah, Raoov, Muggundha
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2021
• Subjects: antifungal agents; Calibration; Capillary electrophoresis; Cyclodextrins; Electrophoresis; Enantiomers; Fungicides; hydroxypropyl‐β‐cyclodextrin; Inclusion complexes; Ketoconazole; Miconazole; Molecular docking; NMR; NMR spectroscopy; Nuclear magnetic resonance; Optimization; Regression analysis; Selectors; Spectrophotometry; Spectroscopy; β-Cyclodextrin; hydroxypropyl-β-cyclodextrin; antifungal agents; molecular docking; capillary electrophoresis; inclusion complexes
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.23285

A chiral separation method coupled with capillary electrophoresis (CE) analysis for ketoconazole and miconazole enantiomers using chiral selectors such as β‐cyclodextrin (β‐CD) and hydroxypropyl‐β‐CD (HP‐β‐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 (β‐CD and HP‐β‐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 (R2 > 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.