Enantioseparation of tetramisole by capillary electrophoresis and high performance liquid chromatography and application of these techniques to enantiomeric purity determination of a veterinary drug formulation of L-levamisole

Abstract

The enantioseparation of the chiral anthelmintic drug tetramisole was studied by capillary electrophoresis using various cyclodextrins as chiral selectors. In particular, the following aspects have been addressed: 1) the enantiomer affinity pattern of tetramisole towards various cyclodextrins; 2) development of a capillary electrophoretic method for quantitative determination of the enantiomeric impurity, i.e. of the R-(+) enantiomer, in S-( -)-tetramisole (levamisole); 3) application of the capillary electrophoretic method for the determination of the enantiomeric impurity of R-(+)-tetramisole in commercial samples and in a veterinary drug formulation of S-( -)-tetramisole; and 4) comparison of capillary electrophoretic and traditional pharmacopoeial polarimetric methods for the enantiomeric impurity determination in S-( -)-tetramisole. Opposite affinity order of tetramisole enantiomers was observed towards different cyclodextrins, depending on the nature of the substituents and the substitution pattern. In addition, an enantioseparation of tetramisole was developed by high performance liquid chromatography on polysaccharide type chiral stationary phase. This method was compared to the aforementioned capillary electrophoretic method. Preliminary validation results indicated that capillary electrophoresis represents a flexible, fast, and inexpensive technique for determination of the enantiomeric impurity of R-(+)-tetramisole in the commercial samples and drug formulations of S-( -)-tetramisole (levamisole). Both of the commercial samples as well as the veterinary drug formulation of levamisole contained R-(+)-tetramisole as enantiomeric impurity. Capillary electrophoresis represents a superior method for enantiomeric impurity determinations compared to the traditional polarimetric method still used in the major pharmacopoeias. CE offers the advantages of miniaturised techniques, as well as higher peak efficiency, flexibility, and shorter method development time compared to HPLC.

Determination of Enantiomeric Compositions of Analytes Using Novel Fluorescent Chiral Molecular Micelles and Steady State Fluorescence Measurements

“…Chiral analysis has previously been achieved using various chiral selectors such as cyclodextrins (CDs) [6][7][8][9][10], antibiotics [11][12][13][14], and crown ethers [15][16][17][18]. However, despite good chiral recognition ability, these chiral selectors have several limitations resulting from low solubility, high cost, and difficult synthetic procedures.…”

Separation of vinca alkaloid enantiomers by capillary electrophoresis applying cyclodextrin derivatives and characterization of cyclodextrin complexes by nuclear magnetic resonance spectroscopy

“…In case of cavity size-dependent reversals intermolecular selector-selectand interactions are the same and the distance between noncovalently interacting groups may change from CD to CD [26][27][28][29]. Introduction of substituents on the CD rims affects the cavity size, as well as the nature of intermolecular forces involved in host-guest interactions and possibly leads to the reversal of the migration order [15,26,[30][31][32][33][34][35][36]. The observation that not only the nature of substituents but also their location on the CD rim may determine the enantiomer affinity pattern of some chiral analytes was made by Tanaka et al [37][38][39] and the phenomenon was confirmed later for acetyl and sulfate groups as substituents by Chankvetadze et al [40,41].…”

Pharmaceutical and biomedical applications of chiral capillary electrophoresis and capillary electrochromatography: An update

“…These include the evaluation of the synthetic process [92,94] as well as the analysis of approved drugs [81][82][83][84][85][86][87][88][89][90]. In several cases, the methods not only allowed the determination of the other enantiomer but also of related substances [84,85,92].…”

“…Chankvetadze and colleagues [87] compared HPLC and CE for the determination of the (R)-enantiomer in levamisole. The resolution was higher for CE using b-CD or HDAS-b-CD as chiral selectors compared to chiral HPLC on a Chiralcel OD column although both methods were suitable to detect the enantiomeric impurity and led to comparable results.…”