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Equilibrium study on enantioselective distribution of amlodipine besilate enantiomers in a biphasic recognition chiral extraction system

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Abstract

The objective of this paper is to present the enantioselective distribution of amlodipine besilate enantiomers (ADB) in a biphasic recognition chiral extraction (BRCE) system. In the BRCE system, hydrophobic tartrate was added in organic phase and hydrophilic β-cyclodextrins in aqueous phase. Tartrate and β-cyclodextrins preferentially recognize (−)-ADB and (+)-ADB, respectively. Impacts of the type and concentration of chiral selectors, the pH value of the aqueous phase solution as well as temperature on the separation efficiency were investigated. Sulfobutyl ether-β-cyclodextrin (SBE-β-CD) and d-isobutyl tartrate (d-IBTA) were found to be the most suitable chiral selectors. By substituting the monophasic recognition chiral extraction (MRCE, with chiral selector in only one phase) system with BRCE system, the distribution ratios of the ADB enantiomers are remarkably increased with a little increase of enantioselectivity. The optimized conditions that are 5 °C of temperature, 7.2 of pH value, 0.05 mol/L of SBE-β-CD as well as 0.1 mol/L of d-IBTA are identified. The experimental results demonstrated that BRCE with strong chiral separation ability possesses good prospect in separation of enantiomers.

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Abbreviations

BRCE:

Biphasic recognition chiral extraction

MRCE:

Monophasic recognition chiral extraction

D :

Distribution ratio, org/aq concentration

P :

Distribution ratios of enantiomers with no chiral selectors

α:

Enantioselectivity

ADB:

Amlodipine

d :

Selector of d-tartaric acid derivative

β-CD:

β-cyclodextrin

References

  1. De Camp, W.H.: The FDA perspective on the development of stereoisomers. Chirality 1, 2–6 (1989)

    Article  Google Scholar 

  2. Hutt, A.J.: Drug chirality: impact on pharmaceutical regulation. Chirality 3, 161–164 (1991)

    Article  CAS  Google Scholar 

  3. Gourlay, M.D., Kendrick, J., Leusen, F.J.J.: Predicting the spontaneous chiral resolution by crystallization of a pair of flexible nitroxide radicals. Cryst. Growth Des. 8, 2899–2905 (2008)

    Article  CAS  Google Scholar 

  4. Miyako, E., Maruyama, T., Kamiya, N., Goto, M.: Highly enantioselective separation using a supported liquid membrane encapsulating surfactant–enzyme complex. J. Am. Chem. Soc. 126, 8622–8623 (2008)

    Article  Google Scholar 

  5. Ward, T.J., Baker, B.A.: Chiral separations. Anal. Chem. 80, 4363–4372 (2008)

    Article  CAS  Google Scholar 

  6. Yu, T., Du, Y., Chen, B.: Evaluation of clarithromycin lactobionate as a novel chiral selector for enantiomeric separation of basic drugs in capillary electrophoresis. Electrophoresis 32, 1898–1905 (2011)

    Article  CAS  Google Scholar 

  7. Afonso, C.A.M., Crespo, J.G.: Recent advances in chiral resolution through membrane-based approaches. Angew. Chem. Int. Ed. 43, 5293–5295 (2004)

    Article  CAS  Google Scholar 

  8. Schuur, B., Verkuijl, B.J.V., Minnaard, A.J., de Vries, J.G., Heeres, H.J., Feringa, B.L.: Chiral separation by enantioselective liquid–liquid extraction. Org. Biomol. Chem. 9, 36–51 (2011)

    Article  CAS  Google Scholar 

  9. Lacour, J., Goujon-Ginglinger, C., Torche-Haldimann, S., Jodry, J.J.: Efficient enantioselective extraction of tris (diimine) ruthenium(II) complexes by chiral, lipophilic TRISPHAT anions. Angew. Chem. Int. Ed. 39, 3695–3697 (2000)

    Article  CAS  Google Scholar 

  10. Tang, K.W., Song, L.T., Liu, Y.B., Pan, Y., Jiang, X.Y.: Separation of flurbiprofen enantiomers by biphasic recognition chiral extraction. Chem. Eng. J. 158, 411–417 (2010)

    Article  CAS  Google Scholar 

  11. Tsukube, H., Shinoda, S., Uenishi, J., Kanatani, T., Itoh, H., Shiode, M., Iwachido, T., Yonemitsu, O.: Molecular recognition with lanthanide (III) tris (beta-diketonate) complexes: extraction transport, and chiral recognition of unprotected amino acids. Inorg. Chem. 37, 1585–1591 (1998)

    Article  CAS  Google Scholar 

  12. Zhang, Y., Hidajat, K., Ray, K.: Enantio-separation of racemic pindolol on 1-acid glycoprotein chiral stationary phase by SMB and varicol. Chem. Eng. Sci. 62, 1364–1375 (2007)

    Article  CAS  Google Scholar 

  13. Tan, B., Luo, G.S., Wang, J.D.: Extractive separation of amino acid enantiomers with co-extractants of tartaric acid derivative and aliquat-336. Sep. Purif. Technol. 53, 330–336 (2007)

    Article  CAS  Google Scholar 

  14. Ding, H.B., Carr, P.W., Cussler, E.L.: Racemic leucine separation by hollow-fiber extraction. AIChE J. 38, 1493–1498 (1992)

    Article  CAS  Google Scholar 

  15. Steensma, M., Kuipers, N.J., De Haan, A.B., Kwant, G.: Influence of process parameters on extraction equilibria for the chiral separation of amines and amino-alcohols with a chiral crown ether. J. Chem. Technol. Biotechnol. 21, 1032–1040 (2006)

    Google Scholar 

  16. Colera, M., Costero, A.M., Gaviñva, P., Gil, S.: Synthesis of chiral 18-crown-6 ethers containing lipophilic chains and their enantiomeric recognition of chiral ammonium picrates. Tetrahedron Asymmetry 16, 2673–2679 (2005)

    Article  CAS  Google Scholar 

  17. Snyder, S.E., Carey, J.R., Pirkle, W.H.: Biphasic enantioselective partitioning studies using small-molecule chiral selectors. Tetrahedron 61, 7562–7567 (2005)

    Article  CAS  Google Scholar 

  18. Kocabas, E., Karakucuk, A., Sirit, A., Yilmaz, M.: Synthesis of new chiral calix[4]arene diamide derivatives for liquid phase extraction of α-amina acid methylesters. Tetrahedron Asymmetry 17, 1514–1520 (2006)

    Article  CAS  Google Scholar 

  19. Keurentjes, J.T.F., Nabuurs, L.W.M., Vegter, E.A.: Liquid membrane technology for the separation of racemic mixtures. J. Membr. Sci. 113, 354–360 (1996)

    Article  Google Scholar 

  20. Franco, P., Blanc, J., Oberleitner, W.R., Maier, N.M., Lindner, W., Minguillón, C.: Enantiomer separation by countercurrent chromatography using cinchona alkaloid derivatives as chiral selectors. Anal. Chem. 74, 4175–4183 (2002)

    Article  CAS  Google Scholar 

  21. Ren, Z., Zeng, Y., Hua, Y., Cheng, Y., Guo, Z.: Enantioselective liquid–liquid extraction of racemic ibuprofen by L-tartaric acid derivatives. J. Chem. Eng. Data 59, 2517–2522 (2014)

    Article  CAS  Google Scholar 

  22. Duret, P., Foucault, A., Margraff, R.: Vancomycin as a chiral selector in centrifugal partition chromatogrphy. J. Liq. Chromatogr. 23, 295–312 (2000)

    Article  CAS  Google Scholar 

  23. Wei, Y., Du, S.J., Ito, Y.: Enantioseparation of lomefloxacin hydrochloride by high-speed counter-current chromatography using sulfated-β-cyclodextrin as a chiral selector. J. Chromatogr. B 878, 2937–2941 (2010)

    Article  CAS  Google Scholar 

  24. Koska, J., Haynes, C.A.: Modelling multiple chemical equilbria in chiral partition systems. Chem. Eng. Sci. 56, 5853–5864 (2001)

    Article  CAS  Google Scholar 

  25. Malta, L.F.B., Cordeiro, Y., Tinoco, L.W., Campos, C.C., Medeiros, M.E., Antunes, O.A.C.: Recognition mechanism of D- and L-tyryptophan enantiomers using 2-hydroxypropyl-α- or β-cyclodextrins as chiral selectors. Tetrahedron Asymmetry 19, 1182–1188 (2008)

    Article  CAS  Google Scholar 

  26. Liu, G., Wang, K., Zhang, M.: Comparative effect of amlodipine and levamlodipine on nocturnal hypertension in hypertensive patients. J. Med. Postgrad. 14, 496–499 (2001)

    Google Scholar 

  27. Ma, Y., Ito, Y., Foucault, A.: Resolution of gram quantities of racemates by high-speed counter-current chromatography. J. Chromatogr. A 704, 75–81 (1995)

    Article  CAS  Google Scholar 

  28. Kuhn, R., Erni, F., Bereuter, T., Haeusler, J.: Chiral recognition and enantiomeric resolution based on host-guest complexation with crown ethers in capillary zone electrophoresis. Anal. Chem. 64, 2815–2820 (1992)

    Article  CAS  Google Scholar 

  29. Cirilli, R., La Torre, F.: Stereoselective analysis of benazepril and its stereoisomers by reversed-phase high-performance liquid chromatography on a chiral AGP column. J. Chromatogr. A 818, 53–60 (1998)

    Article  CAS  Google Scholar 

  30. Heldin, E., Lindner, K.J., Pettersson, C., Lindner, W., Rao, R.: Tartaric acid derivatives as chiral selectors in liquid chromatography. Chromatographia 32, 407–416 (1992)

    Article  Google Scholar 

  31. Xie, J., Tan, Q., Yang, L., Lai, S., Tang, S., Cai, C., Chen, X.: A simple and rapid method for chiral separation of amlodipine using dual chiral mobile phase additives. Anal. Methods 6, 4408–4413 (2014)

    Article  CAS  Google Scholar 

  32. Taraszewska, J.: Complexes of β-cyclodextrin with chloronitrobenzenes and with solvents in water + organic solvent mixtures. J. Incl. Phenom. Mol. Recognit. Chem. 10, 69–78 (1991)

    Article  CAS  Google Scholar 

  33. O’Brien, T., Crocker, L., Thompson, R., Thompson, K., Tom, P.H., Conlon, D.A., Feibush, B., Moeder, C., Bicker, G., Grinberg, N.: Mechanistic aspects of chiral discrimination on modified cellulose. Anal. Chem. 69, 1999–2007 (1997)

    Article  Google Scholar 

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Acknowledgments

This work was supported by the National Science Foundation of China (No. 21501057), the planned Science and Technology project of Hunan Province, China (No. 2013SK3166), and Aid program for Science, construct program of the key discipline in Hunan province, and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province.

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Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, Hunan, China

    Panliang Zhang & Yunren Qiu

  2. Department of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, 414006, Hunan, China

    Panliang Zhang, Genlin Sun, Kewen Tang, Congshan Zhou & Changan Yang

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  1. Panliang Zhang
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  2. Genlin Sun
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Correspondence to Yunren Qiu or Kewen Tang.

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Zhang, P., Sun, G., Qiu, Y. et al. Equilibrium study on enantioselective distribution of amlodipine besilate enantiomers in a biphasic recognition chiral extraction system. J Incl Phenom Macrocycl Chem 85, 127–135 (2016). https://doi.org/10.1007/s10847-016-0612-5

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  • DOI: https://doi.org/10.1007/s10847-016-0612-5

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