Enantioseparation of meptazinol and its three intermediate enantiomers by capillary electrophoresis using a new cationicβ‐cyclodextrin derivative in single and dual cyclodextrin systems

Abstract

A new cationic β-cyclodextrin derivative, mono-6-deoxy-6-piperdine-β-cyclodextrin (PIP-β-CD), was synthesized and applied as a chiral selector for the enantioseparation of meptazinol and its three intermediate enantiomers (intermediates II-IV) in capillary electrophoresis. When PIP-β-CD was employed as the single CD system, intermediate II was baseline enantioseparated while the results for the other analytes were less satisfactory. In order to enhance the selectivity and resolution of meptazinol intermediate III and intermediate IV, dual CD systems of PIP-β-CD in combination with three different neutral CDs were synthesized and tested: β-cyclodextrin (β-CD), trimethyl-β-cyclodextrin (TM-β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). After investigating the effect on the enantioseparation efficiency of the nature and the concentration of both CDs, the dual CD system consisting of PIP-β-CD and HP-β-CD was shown to be the most efficient for the simultaneous enantioseparation of meptazinol intermediates III and IV.

Recent development of cationic cyclodextrins for chiral separation

“…The limit of quantification (LOQ) was obtained an accuracy of 0.05 µM for D-serine and D-aspartate. Chiral separation of meptazinol and three intermediate enantiomers was realized using cationic PIPCD in single and dual CD systems by CE [36]. The dual system containing PIPCD and HPrAMCD proved to be the most efficient for simultaneous separation of 3-(3-hydroxy-phenyl)-1-methyl-azepan-2-one and 3-ethyl-3-(3-hydroxyphenyl)-1-methyl-azepan-2-one.…”

Chiral selectors in CE: Recent development and applications (mid‐2014 to mid‐2016)

“…In 2015, Yu et al. synthesized and used PIP‐β‐CD as a CS for the separation of meptazinol and its three intermediate enantiomers (intermediate II, intermediate III, and intermediate IV). When 12.5 mM PIP‐β‐CD was used, only the enantiomers of intermediate II were able to be baseline separated.…”

Recent advances in capillary electrophoretic migration techniques for pharmaceutical analysis (2013–2015)

“…Analyzing commercial injection solutions, concentrations of 100.7 ± 1.1 % for levosulpiride and 0.27 ± 0.02 % for R ‐sulpiride were found. A dual CD system composed of HP‐β‐CD and mono‐6‐deoxy‐6‐piperidine‐β‐CD in 20 mM sodium phosphate BGE, pH 3.0, was developed for the simultaneous enantioseparation of meptazinol and two chiral synthetic intermediates but not applied to the determination of the chiral purity of the compound . Lipka and colleagues achieved the enantioseparation of several agomelatine analogs using a combination of the negatively charged highly sulfated γ‐CD and the positively charged 6‐monodeoxy‐6‐monoamino‐β‐CD in a 25 mM sodium phosphate buffer, pH 2.5 .…”