Enantioseparation of Three Non-Steroidal Anti-Inflammatory Agents on Chiral Stationary Phase by HPLC


This paper reported the enantioseparation of Naproxen, Ketoprofen and Etodolac on tartardiamide-DMB chiral stationary phase (CHI-DMB) and (R,R) –DNB-DPEDA chiral stationary phase,using hexane as the mobile phase with various modifiers. The influence of the mobile phase composition including the type and concentration of the modifiers in hexane and the structures of the analytes on the chiral separation was studied. The results indicated that the steric structure of the solute, especially the environment of the chiral carbon, was the predominant factor for the chiral recognition. The type, the steric structure and the concentration of the modifiers also influence the retention factor and the resolution. The chiral recognition mechanism of the analytes on CHI-DMB and (R,R) –DNB-DPEDA was also discussed. The hydrogen-bonding interaction played an important role on enantioseparation on CHI-DMB, so did the π-π interaction. On (R,R) –DNB-DPEDA the π-π interaction was the key for the solutes retention and enantioseparation, while hydrogen-bonding interaction was not important. Additionally, it has been demonstrated that enantioselectivity and retention was also dependent upon the nature and functional groups on the aromatic ring of solutes and CSP.

Share and Cite:

X. Zhang, Z. Li, B. Shen, J. Chen and X. Xu, "Enantioseparation of Three Non-Steroidal Anti-Inflammatory Agents on Chiral Stationary Phase by HPLC," Journal of Analytical Sciences, Methods and Instrumentation, Vol. 2 No. 1, 2012, pp. 18-23. doi: 10.4236/jasmi.2012.21004.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] L. Asnin, F. Gritti, K. Kaczmarski and G. Guiochon, “Features of the Adsorption of Naproxen on the Chiral Stationary Phase (S,S)-Whelk-O1 under Reversed-Phase Conditions,” Journal of Chromatography A, Vol. 1217, No. 3, 2010, pp. 264-275.
[2] J. J. Ha, H. J. Choi, J. S. Jin, E. D. Jeong and M. H. Hyun, “Liquid Chromatographic Resolution of Proton Pump Inhibitors Including Omeprazole on a Ligand Exchange Chiral Stationary Phase,” Journal of Chromatography A, Vol. 1217, No. 41, 2010, pp. 6436-6441. doi:10.1016/j.chroma.2010.08.041
[3] K. Si-Ahmed, F. Ta-zerouti, A. Y. Badjah-Hadj-Ahmed, Z. Aturki and G. D’Orazio, “Optical Isomer Separation of Flavanones and Flavanone Gly-cosides by Nano-Liquid Chromatography Using a Phenyl-Carbamate-Propyl-β-Cyclodextrin Chiral Stationary Phase,” Journal of Chromatography A, Vol. 1217, No. 7, 2010, pp. 1175-1182. doi:10.1016/j.chroma.2009.07.053
[4] L. L. Zhou, B. Mao and Z. H. Ge, “Comparative Study of Immobilized α1 Acid Glycoprotein and Ovomucoid Protein Stationary Phases for the Enantiomeric Separation of Pharmaceutical Compounds,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 46, No. 5, 2008, pp. 898-906. doi:10.1016/j.jpba.2007.07.008
[5] L. M. Peng, S. Jayapalan, B. Chankvetadze and T. Farkas, “Reversed-Phase Chiral HPLC and LC/MS Analysis with tris(Chloromethylphenylcarbamate) Derivatives of Cellulose and Amylose as Chiral Stationary Phases,” Journal of Chromatography A, Vol. 1217, No. 44, 2010, pp. 6942-6955. doi:10.1016/j.chroma.2010.08.075
[6] J. Oxelbark and P. Gidlund, “Investigation of a Tartaric Acid-Based Linear Polyamide and Dimer as Chiral Selectors in Liquid Chromatography,” Chirality, Vol. 17, No. 2, 2005, pp. 79-84. doi:10.1002/chir.20106
[7] H. Y. Aboul-Enein, “Chiral Resolution of Some Piperidine 2,6-dione Drugs by High Performance Liquid Chromatography on Kromasil? CHI-DMB Column,” Archiv der Pharmazie, Vol. 337, No. 8, 2004, pp. 453- 456. doi:10.1002/ardp.200300857
[8] Y. F. Liu, C. P. Zhai, M. H. Zhou, J. G. Zheng, Q. Xiao, Q. Z. Li, D. Li, D. H. Xiao and D. L. Yue, “Direct Resolution of Diniconazole Optical Isomers on Chiralcel Acylamide Column,” Journal of Instrumental Analysis, Vol. 28, No. 10, 2009.
[9] B. Kosjek and G. Uray, “Im-mobilization of Difunctional Building Blocks on Hydroxysuc-cinimide Activated Silica: Versatile in Situ Preparation of Chiral Stationary Phases,” Chirality, Vol. 13, No. 10, 2001, pp. 657-667. doi:10.1002/chir.10020
[10] D. M. Forjan, D. Kontrec and V. Vinkovi?, “Performance of Brush-Type HPLC chiral Stationary Phases with Tertiary Amide in the Connecting Tether,” Chirality, Vol. 18, No. 10, 2006, pp. 857-869. doi:10.1002/chir.20329
[11] B. C. Shen, X. Z. Xu, X. J. Zhang and J. J. Chen, “Enantioseparation and Chiral Recognition Me-chanism of Two Novel Organic Phosphonate Derivatives on Chiral Stationary Phases,” Analytical Letters, Vol. 38, 2005, pp. 1317-1330.
[12] W.-J. Wei, H.-W. Deng, W. Chen, Z.-W. Bai and S.-R. Li, “Preparation and Enantioseparation of a Mixed Selector Chiral Stationary Phase Derived from Benzoylated Tar-taric Acid and 1,2-Diphenylethylenediamine,” Chirality, Vol. 22, No. 6, 2010, pp. 604-611.
[13] A. Campiglio, “Determination of Naproxen with Chemiluminescence Detection,” Analyst, Vol. 123, 1998, pp. 1571-1574. doi:10.1039/a802013b
[14] F. Lelievre and P. Gareil, “Chiral Separations of Underivatized Arylpropionic Acids by Capillary Zone Electrophoresis with Various Cyclodextrins Acidity and Inclusion Constant Determinations,” Journal of Chromatography A, Vol. 735, No. 1-2, 1996, pp. 311-320. doi:10.1016/0021-9673(95)00745-8
[15] J. M. Shi and D. Li, Chinese Journal of Clinical Pharmacy, Vol. 9, 2000, pp. 321-324.
[16] D. M. Chen, Q. Fu, N. Li, S. X. Zhang and Q. Q. Zhang, Chinese Journal of Chemistry, Vol. 35, No. 1, 2007, pp. 75-78.
[17] K. W. Tang, P. L. Zhang, C. Y. Pan and H. J. Li, “Modeling Multiple Chemical Equilibrium for Reactive Extrac-tion of Naproxen Enantiomers with HP-β-CD as Hydrophilic Selector,” Science China Chemistry, Vol. 54, No. 7, 2011, pp. 1130-1137.
[18] Q. Tang, X. Y. Chen and H. Song, Chinese Journal of Chemistry, Vol. 35, No. 2, 2007, pp. 240-243.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.