Enantiomeric Separation of Nefopam Hydrochloride by Affinity Electrokinetic Chromatography Using Chondroitin Sulfate A as Chiral Selector and Its Chiral Recognition Mechanism

Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing, 210009 China; Key Laboratory of Modern Chinese Medicines (Ministry of Education), China Pharmaceutical University, Nanjing, 210009 China
Chromatographia (Impact Factor: 1.44). 72(5):489-493. DOI: 10.1365/s10337-010-1670-2

ABSTRACT In this study, a new approach to the enantioseparation of nefopam hydrochloride by means of affinity electrokinetic chromatography
(AEKC) with chondroitin sulfate A belonging to linear ionic polysaccharides has been developed. The difference in the antinociceptive
activity of the enantiomers of nefopam was demonstrated in some studies, and the method established in this paper allowed
complete separation of nefopam. Especially, there are no reports concerned with the enantioselective separation of nefopam
using chondroitin sulfate A as chiral selectors in CE. During the course of this work, both migration time and enantioseparation
of nefopam were influenced by several parameters such as pH of the BGE, selector concentration, capillary temperature and
applied voltage. Consequently, these parameters were systematically optimized in order to obtain the optimum enantioseparation
of nefopam. Moreover, comparison of the influences of the studied parameters was further investigated using univariate analysis
of variance as a calculation method by Statistical Product and Service Solutions (SPSS) in this paper. Finally, a mechanism
of enantiorecognition in AEKC towards the enantiomers of nefopam with chondroitin sulfate A was described.

KeywordsAffinity electrokinetic chromatography-Enantiomeric separation-Polysaccharides-Nefopam hydrochloride-Chondroitin sulfate A

  • [Show abstract] [Hide abstract]
    ABSTRACT: Various chiral selectors have been employed in CE and among them linear polysaccharides exhibited powerful enantioselective properties. Different from linear polysaccharides, the use of branched polysaccharides as chiral selectors in CE has not been reported previously. In this study glycogen belonging to the class of branched polysaccharides was used as a novel chiral selector for the enantiomeric separations for the first time. Since glycogen is electrically neutral, the method is applicable to ionic compounds. Eighteen chiral compounds including 12 basic drugs and six acidic drugs have been tested to demonstrate the potential of this chiral selector. BGE and selector concentrations and buffer pH were systematically optimized in order to obtain successful chiral separations. Among the tested compounds, the enantiomers of ibuprofen, which is an acidic drug, were successfully recognized by 3.0% w/v glycogen with 90 mM Tris-H(3)PO(4) buffer (pH 7.0). The enantiomers of basic drugs such as citalopram, cetirizine and nefopam were also baseline-resolved with 50 mM Tris-H(3)PO(4) buffer (pH 3.0) containing 3.0% glycogen. Amlodipine belonging to basic compound only gave partial enantioseparation under the above-mentioned condition.
    Electrophoresis 03/2010; 31(6):1044-50. · 3.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This review gives an overview of recent developments in CZE, EKC, and CEC covering the literature since the year 2004. Since there appeared a special issue on applications, this review focuses on the progress in electromigration techniques and new methodological developments. New techniques, new chiral selectors as well as new chiral stationary phases for CEC are discussed.
    Electrophoresis 02/2007; 28(1-2):114-26. · 3.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Polygalacturonic acid, a linear high molecular weight homopolysaccharide was investigated as a chiral selector in capillary zone electrophoresis for the separation of enantiomers of basic drugs. The choices of running buffer pH and concentration of chiral selector were found to be important for the improvement of enantioselectivity. The effects of background electrolyte concentration and the capillary temperature on the separation were also examined. Enantioseparations were carried out in the acidic conditions using 1.5% polygalacturonic acid (w/v) in a 40mM phosphate buffer under an applied voltage of 15kV. The optimization of these separations was dependent on the nature of the analytes and could be achieved by the proper choice of experimental conditions. A brief mechanism of enantiorecognition by polygalacturonic acid was also given.
    Chromatographia 69(11):1315-1320. · 1.44 Impact Factor