A novel design of simulated moving bed (SMB) chromatography for separation of ketoprofen enantiomer

  • Tae Ho Yoon
  • Bong Hyun Chung
  • In Ho Kim


A simulated moving bed (SMB) chromatography system is a powerful tool for preparative scale separation, which can be applied to the separation of chiral compound. We have designed our own lab-scale SMB chromatography using 5 HPLC pumps, 6 stainless steel columns and 4 multi-position valves, to separate a racemic mixture of ketoprofen in to its enantiomers. Our design has the characteristics of the low cost for assembly for the SMB chromatography and easy repair of the unit, which differs from the designs suggested by other investigators. It is possible for the flow path through each column to be independently changed by computer control, using 4 multi-position rotary valves and 5 HPLC solvent delivery pumps. In order to prove the operability of our SMB system, attempts were made to separate the (S)-ketoprofen enantiomer from a ketoprofen racemic mixture. The operating parameters of the SMB chromatography were calculated for ketoprofen separation from a batch chromatography experiment as well as by the triangle theory. With a feed concentration of 1 mg/mL, (S)-ketoprofen was obtained with a purity of 96% under the calculated operating conditions.


SMB chromatography rotary valve chiral separation ketoprofen enantiomer 


  1. [1]
    Pais, L. S., J. M. Loureiro, and A. E. Rodrigues (2000) Chiral separation by the SMB chromatography.Sep. Purif. Technol. 20: 66–77.CrossRefGoogle Scholar
  2. [2]
    Wankat, P. C. (2001) Simulated moving bed cascade for ternary separations.Ind. Eng. Chem. Res. 40: 6185–6193.CrossRefGoogle Scholar
  3. [3]
    Broughton, D. B. (1961) Continuous sorption process employing fix bed of sorbent and moving inlet and outlets.US Patent 2,985,589.Google Scholar
  4. [4]
    Biressi, G., O. L. Hombourger, M. Mazzotti, R. M. Nicoud, and M. Morbidelli (2000) Design and optimization of a simulated moving bed unit; Role of deviation from equilibrium theory.J. Chromatogr. A 876: 3–15.CrossRefGoogle Scholar
  5. [5]
    Schulte, M. and J. Strube (2001) Preparative enantio separation by simulated moving bed chromatography.J. Chromatogr. A 906: 399–416.CrossRefGoogle Scholar
  6. [6]
    Row, K. H., C. H. Lee, and J. H. Kang (2002) Parameter estimation of perillyl alcohol in RT-HPLC by moment analysis.Biotechnol. Bioprocess Eng. 7: 16–20.CrossRefGoogle Scholar
  7. [7]
    Li, C., W.-C. Lee, and K. H. Lee (2003) Affinity separations using microfabricated microfluidic devices:In situ photopolymerization and use in protein separations.Biotechnol. Bioprocess Eng. 8: 240–245.CrossRefGoogle Scholar
  8. [8]
    Chaton, F., M. Bailly, and G. Guiochon (1994) Recycling in preparative liquid chromatography.J. Chromatogr. A 687: 12–31.Google Scholar
  9. [9]
    Kubota, K. and S. Hayashi (1994) Preparative chromatographic separation with moving feed port.J. Chromatogr. A 658: 259–270.CrossRefGoogle Scholar
  10. [10]
    Heuer, C., A. Seidel-Morgenstern, and P. Hugo (1995) Experimental investigation and modeling of closed-loop recycling in preparative chromatography.Chem. Eng. Sci. 50: 1115–1127.CrossRefGoogle Scholar
  11. [11]
    Ouinones, I., C. M. Grill, L. Miller, and G. Guiochon (2000) Modeling of separation by closed-loop steady-state recycling of a racemic pharmaceutical intermediate.J. Chromatogr. A 867: 1–21.CrossRefGoogle Scholar
  12. [12]
    Huthman, E. and M. Juza (2001) Modification of a commercial chiral stationary phase: Influences on enantiomer separations using simulated moving bed chromatography.J. Chromatogr. A 908: 185–200.CrossRefGoogle Scholar
  13. [13]
    Guest, D. W. (1997) Evaluation of simulated moving bed chromatography for pharmaceutical process development.J. Chromatogr. A 760: 159–162.CrossRefGoogle Scholar
  14. [14]
    Jalon, E. G., M. Josam, M. A. Campanero, S. Santoyo, and P. Ygartua (2000) Determination by high performance liquid chromatography of ketoprofenin vitro in rat skin permeation samples.J. Chromatogr. A 870: 143–149.CrossRefGoogle Scholar
  15. [15]
    Perrin, C., N. Matthijs, D. Mangelins, C. Granier-Loyaux, M. Maftouh, D. L. Massart, and Y. V. Heyden (2002) Screening approach for chiral separation of pharmaceuticals part II. Reversed liquid chromatography.J. Chromatogr. A 966: 119–134.CrossRefGoogle Scholar
  16. [16]
    Pais, L. S. and A. E. Rodrigues (2003) Design of simulated moving bed and Varicol processes for preparative separations with a low number of columns.J. Chromatogr. A 1006: 33–44.CrossRefGoogle Scholar
  17. [17]
    Mazzotti, M., G. Storti, and M. Morbidelli (1997) Optimal operation of simulated moving bed unit for nonlinear chromatographic separations.J. Chromatogr. A 769: 3–24.CrossRefGoogle Scholar
  18. [18]
    Juza, M. (1999) Development of a high performance liquid chromatographic simulated moving bed separation from an industrial perspective.J. Chromatogr. A 865: 35–49.CrossRefGoogle Scholar

Copyright information

© The Korean Society for Biotechnology and Bioengineering 2004

Authors and Affiliations

  1. 1.Department of Chemical EngineeringChungnam National UniversityDaejeonKorea
  2. 2.Laboratory of Integrative BiotechnologyKorea Research Institute of Bioscience and BiotechnologyDaejeonKorea

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