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

Abstract

Ondansetron, a highly selective 5‐hydroxytryptamine 3 receptor antagonist, was successfully enantioseparated by recycling countercurrent chromatography using sulfobutyl ether‐β‐cyclodextrin as chiral selector. Important factors for the enantioseparation were optimized, including different organic solvent, type of substituted β‐cyclodextrin, pH of aqueous phase, concentration of chiral selector, and separation temperature. A biphasic solvent system composed of n‐hexane: n‐butyl acetate: 0.1 mol/L phosphate buffer solution pH 9.2 with 50 mmol/L of sulfobutyl ether‐β‐cyclodextrin (2.5:7.5:10, v/v/v) was selected. Under optimized separation conditions, 5 mg of ondansetron was enantioseparated using recycling countercurrent chromatography, yielding 1.2 and 1.5 mg of ondansetron enantiomers with 97.5 and 95.8% purity and the recovery reached 48–60%.

An overview of chiral separations of pharmaceutically active substances by HPLC (2018–2020)

“…Successful preparative separation of 2-(4-bromomethylphenyl)propionic acid enantiomers, one of which is a precursor for further synthesis of chiral loxoprofen, was reported using hydroxypropyl-β-CD CS added to the aqueous phase by counter current chromatography [ 16 ]. An effective antiemetic drug ondansetron was also enantioseparated by counter current chromatography with sulfobutyl ether β-CD as a CS [ 17 ].…”

Enantioseparation of N‐methyl duloxetine, duloxetine, and fluoxetine by countercurrent chromatography using anionic β‐cyclodextrin as chiral selector

“…Anionic β‐cyclodextrin was considered to be an efficient chiral selector for enantioseparation of basic compounds in HPLC and CE [29–34], which showed impressive high enantiorecognition due to its strong electrostatic interactions. In our recent work, SBE‐β‐CD was applied to the countercurrent chromatographic enantioseparation of N ‐alkyl alkaline drug ondansetron [35]. In our present work, N ‐methyl duloxetine, duloxetine, and fluoxetine (Figure 1) were enantioseparated by countercurrent chromatography using two anionic β‐cyclodextrins as chiral selectors.…”

“…Therefore, the ionization of enantiomers should be suppressed. A low pH value would be preferable for acidic analytes, while an alkaline pH value would be selected for basic enantiomers to ensure a high enantiorecognition [19][20][21][22][23][24][25][26][27]35]. In the present study, a range of pH 5.6-9.2 was investigated.…”

Vortex‐assisted dispersive solid‐phase microextraction of ondansetron and domperidone using carbonized cockle shell modified with nitrogen and sulfur‐doped carbon dots as a bio‐based sorbent

“…Various literature has been utilized to determine ON and DP in drug products and biological fluid samples, including spectroscopy, electrochemical approach, and chromatography [12][13][14]. Researchers currently aim to provide methods that have advantages such as high sensitivity, fast response, low cost, environmental adaptability, and exceptional simplicity.…”