Abstract
A chiral mobile phase HPLC method is described for chiral separation and determination of chlorpheniramine (CP) enantiomers in various commercial preparations. Chromatographic separation was achieved on a conventional ODS column with a mixture of aqueous sodium phosphate (5 mM) containing 0.5 mM carboxymethyl-β-cyclodextrin, methanol and triethylamine (73:25:2, v/v/v, pH 4.3) as the mobile phase. The flow rate of isocratic elution was 0.24 mL/min and peaks were detected at 224 nm. The method was applied to nine commercial CP preparations in six dosage forms and CP enantiomers were well separated without any disturbance of other ingredients or impurities present. The results showed that only one preparation was d-CP and the others were dl-CP preparations. The contents of all the preparations were found to be in the range of 97%–104% of labeled contents. This method was economical and convenient, affording sufficient accuracy, precision and reproducibility, as well as sensitivity and selectivity.
Similar content being viewed by others
References
Agyei, N. M., Gahm, K. H., and Stalcup, A. M., Chiral separations using heparin and dextran sulfate in capillary zone electrophoresis. Anal. Chim. Acta, 307, 185–191 (1995).
Baumy, Ph., Morin, Ph., Dreux, M., Viaud, M. C., Boye, S., and Guillaumet, G., Determination of β-cyclodextrin inclusion complex constants for 3,4-dihtdro-2H-1-benzopyran enantiomers by capillary electrophoresis. J. Chromatogr. A, 707 311–326 (1995).
Bressolle, F., Audran, M., Pham, T. N., and Vallon, J. J., Cyclodextrins and enantiomeric separations of drugs by liquid chromatography and capillary electrophoresis: basic principles and new developments. J. Chromatogr. B, 687, 303–336 (1996).
Chang, R. S. L., Tran, V. T., and Snyder, S. H., Characteristics of histamine H1-receptors in peripheral tissues labeled with [3H]-mepyramine. J. Pharmacol. Exp. Ther., 209, 437–442 (1979).
Chankvetadze, B., Burjanadze, N., Maynard, D. M., Bergander, K., Bergenthal, D., and Blaschke, G., Comparative enantioseparations with native β-cyclodextrin and heptakis-(2-O-methyl-3,6-di-O-sulfo)-β-cyclodextrin in capillary electrophoresis. Electrophoresis, 23, 3027–3034 (2002).
De Beer, J. O., Vandenbroucke, C. V., Massart, D. L., and De Spiegeleer, B. M., Half-fraction and full factorial designs versus central composite design for retention modelling in reversed-phase ion-pair liquid chromatography. J. Pharm. Biomed. Anal., 14, 525–541 (1996).
Fried, K. M., Young, A. E., Yasuda, S. U., and Wainer, I. W., The enantioselective determination of chlorpheniramine and its major metabolites in human plasma using chiral chromatography on a b-cyclodextrin chiral stationary phase and mass spectrometric detection. J. Pharm. Biomed. Anal., 27, 479–488 (2002).
Gottia, R., Cavrini, V., Andrisanoa, V., and Mascellani, G., Semisynthetic chondroitins as chiral buffer additives in capillary electrophoresis. J. Chromatogr. A, 845, 247–256 (1999).
Haginaka, J. and Kagawa, C., Retentivity and enantioselectivity of uniformly sized molecularly imprinted polymers for d-chlorpheniramine and l-chlorpheniramine in hydro-organic mobile phases. J. Chromatogr. B, 804, 19–24 (2004).
Haginaka, J. and Kagawa, C., Uniformly sized molecularly imprinted polymer for d-chlorpheniramine: Evaluation of retention and molecular recognition properties in an aqueous mobile phase. J. Chromatogr. A, 948, 77–84 (2002).
Haginaka, J., Kagawa, C., and Matsunaga, H., Separation of enantiomers on a chiral stationary phase based on ovoglycoprotein. VII. Comparison of chiral recognition ability of ovoglycoprotein from chicken and Japanese quail egg whites. J. Chromatogr. A, 858, 155–165 (1999).
Haginaka, J. and Kanasugi, N., Separation of basic drug enantiomers by capillary zone electrophoresis using ovoglycoprotein as a chiral selector. J. Chromatogr. A, 782, 281–288 (1997).
Hiep, B. T., Khanh, V., Hung, N. K., Thuillier, A., and Gimenez, F., Determination of the enantiomers of chlorpheniramine and its main monodesmethyl metabolite in urine using achiral-chiral liquid chromatography. J. Chromatogr. B, 707, 235–240 (1998).
Jin, L. J. and Li, S. F. Y., Comparison of chiral recognition capabilities of cyclodextrins for the separation of basic drugs in capillary zone electrophoresis. J. Chromatogr. B Biomed. Sci. Appl., 708, 257–266 (1998).
Koch, K. M., O’Connor-Semmes, R. L., Davis, I. M., and Yin, Y., Stereoselective pharmacokinetics of chlorpheniramine and the effect of ranitidine. J. Pharm. Sci., 87, 1097–1100(1998).
Makamba, H., Andrisano, V., Gotti, R., Cavrini, V., and Felix, G., Sparteine as mobile phase modifier in the chiral separation of hydrophobic basic drugs on an α1-acid glycoprotein column. J. Chromatogr. A, 818, 43–52 (1998).
Matsunaga, H., Tanimoto, T., and Haginaka, J., Separation of basic drug enantiomers by capillary electrophoresis using methylated glucuronyl glucosyl β-cyclodextrin as a chiral selector. J. Sep. Sci., 25, 1175–1182 (2002).
Olmo, B., García, A., Marín, A., and Barbas, C., New approaches with two cyano columns to the separation of acetaminophen, phenylephrine, chlorpheniramine and related compounds. J. Chromatogr. B, 817, 159–165 (2005).
Sakurai, E., Yamasaki, S., Iizuka, Y., Hikichi, N., and Niwa, H., The optical resolution of racemic chlorpheniramine and its stereoselective pharmacokinetics in rat plasma. J. Pharm. Pharmacol., 44, 44–47 (1992).
Scott R. L., Some comments on the Benesi-Hildebrand equation. Rec. Trav. Chim., 75, 787–789 (1956).
Stalcup, A. M. and Gahm, K. H., Applications of sulfated cyclodextrins to chiral separations by capillary zone electrophoresis. Anal. Chem., 68, 1360–1368 (1996).
Sun, S. W. and Lin, Y. R., Optimization of capillary electrophoretic separation of chlorpheniramine enantiomers by a Plackett-Burman design. Determination of enantiomeric purity of dexchlorpheniramine. J. Liq. Chromatogr. Rel. Tech., 24, 2051–2066 (2001).
Tran, V. T., Chang, R. S. L., and Snyder, S. H., Histamine H1 receptors identified in mammalian brain membranes with [3H]-mepyramine. Proc. Natl. Acad. Sci., 75, 6290–6294 (1978).
Van Eeckhaut, A., Detaevernier, M. R., and Michotte, Y., Development of a validated capillary electrophoresis method for enantiomeric purity testing of dexchlorpheniramine maleate. J. Chromatogr. A, 958, 291–297 (2002).
Wind, M., Hoffmann, P., Wagner, H., and Thormann, W., Chiral capillary electrophoresis as predictor for separation of drug enantiomers in continuous flow zone electrophoresis. J. Chromatogr. A, 895, 51–65 (2000).
Wu, H. L., Huang, C. H., Chen, S. H., and Wu, S. M., Chiral quantitation of pheniramine chlorpheniramine and brompheniramine maleates by capillary zone electrophoresis. J. Chromatogr. Sci., 37, 24 (1999).
Xu, H., Yu, X., and Chen, H., Enantiomeric separation of basic drugs with partially filled serum albumin as chiral selector in capillary electrophoresis. Anal. Sci., 20, 1409–1413 (2004).
Yasuda, S. U., Zannikos, P., Young, A. E., Fried, K. M., Wainer, I. W., and Woosley, R. L., The roles of CYP2D6 and stereoselectivity in the clinical pharmacokinetics of chlorpheniramine maleate. Br. J. Clin. Pharmacol., 53, 519–525 (2002).
Yuan, L., Liu, J., Yan, Z., Ai, P., Meng, X., and Xu, Z., Enantioseparation of chlorpheniramine by high speed countercurrent chromatography using carboxymethyl-β-cyclodextrin as chiral selector. J. Liq. Chromatogr. Rel. Tech., 28, 3057–3063 (2005).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chen, Q.C., Jeong, S.J., Hwang, G.S. et al. Enantioselective determination of chlorpheniramine in various formulations by HPLC using carboxymethyl-β-cyclodextrin as a chiral additive. Arch. Pharm. Res. 31, 523–529 (2008). https://doi.org/10.1007/s12272-001-1188-3
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-001-1188-3