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Enantiomeric Resolution of Drug Compounds by Liquid Chromatography

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Abstract

Novel techniques have recently emerged to separate chiral drug compounds into pure enantiomers. The mechanism, experimental difficulties, and applicability of these methods can vary greatly, and the choices involved are not straightforward. The most significant new advances in the field of chiral separations have come from work done with liquid chromatographic systems and chiral stationary-phase columns. This review describes several commonly used approaches to chiral separation, diastereomeric derivatization, chiral mobile-phase additives, and three major types of chiral stationary phases. Although no single method can be judged superior for every drug application, it appears that chiral stationary phases have received the most attention recently and they are emphasized here.

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REFERENCES

  1. R. Bishop, I. Hermansson, B. Jaderlund, G. Lindgren, and C. Pernow. Am. Lab. 18:138–144 (1986).

    Google Scholar 

  2. W. L. Hinze and D. W. Armstrong. Anal. Lett. 13:103–104 (1980).

    Google Scholar 

  3. D. W. Armstrong. Anal. Chem. 59:84A–91A (1987).

    Google Scholar 

  4. E. Gil-Av and D. Nurok. In J. C. Giddings and R. A. Keller (eds.), Advances in Chromatography, Marcel Dekker, New York, 1974, Vol. 10 pp 99–172.

    Google Scholar 

  5. H. C. Rose, R. L. Stern, and B. L. Krager. Anal. Chem. 38:469–472 (1966).

    Google Scholar 

  6. W. H. Pirkle and J. R. Hauske. J. Org. Chem. 42:1839–1844, 2436–2439 (1977).

    Google Scholar 

  7. W. H. Pirkle and J. Finn. In J. D. Morrison (ed.), Asymmetric Synthesis, Vol. 1. Analytical Methods, Academic Press, New York, 1983, pp. 87–124.

    Google Scholar 

  8. R. W. Souter, Chromatographic Separations of Stereoisomers, CRC Press, Boca Raton, Fla., 1985.

    Google Scholar 

  9. W. Linder and C. Petterson. In I. W. Wainer (ed.), Liquid Chromatography in Pharmaceutical Development: An Introduction, Aster, Springfield, Ore., 1985, pp 63–131.

    Google Scholar 

  10. B. Testa. Xenobiotica 16:265–279 (1986).

    Google Scholar 

  11. A. A. Gulaid, G. W. Houghton, and A. R. Boobis. J. Chromatogr. 318:393–397 (1985).

    Google Scholar 

  12. M. J. Wilson and T. Walle. J. Chromatogr. 310:424–430 (1984).

    Google Scholar 

  13. P. H. Hsyu and K. M. Giacomini. J. Pharm. Sci. 75:601–605 (1986).

    Google Scholar 

  14. A. J. Sedman and J. Gal. J. Chromatogr. 278:199–203 (1983).

    Google Scholar 

  15. M. Yoneda, A. Shiratsuchi, M. Yoshimura, Y. Ohkawa, and T. Muramatsu. Chem. Pharm. Bull. 33:2735–2742 (1985).

    Google Scholar 

  16. C. Banfield and M. Rowland. J. Pharm. Sci. 72:921–924 (1983).

    Google Scholar 

  17. D. M. Johnson, A. Reuter, J. M. Collins, and G. F. Thompson. J. Pharm. Sci. 68:112–114 (1979).

    Google Scholar 

  18. J. P. Kamerling, M. Duran, G. J. Gerwig, D. Ketting, L. Brunvis, J. F. G. Vliegenthart, and S. K. Wadman. J. Chromatogr. 222:276–283 (1981).

    Google Scholar 

  19. I. S. Krull. In J. C. Giddings, E. Grushka, J. Cazes, and P. R. Brown (eds.), Advances in Chromatography, Vol. 16, J. B. Lippincott, Philadelphia, 1977, pp. 175–210.

    Google Scholar 

  20. H. Nakazawa and H. Yoneda. J. Chromatogr. 160:89–99 (1978)

    Google Scholar 

  21. J. Lepage, W. Lindner, G. Davies, and B. Karger. Anal. Chem. 51:433–435 (1979).

    Google Scholar 

  22. C. Pettersson and G. Schill. J. Chromatogr. 204:179–183 (1981).

    Google Scholar 

  23. J. Lepage, W. Lindner, G. Davies, and B. Karger. J. Chromatogr. 185:323–344 (1979).

    Google Scholar 

  24. C. Gilon, R. Leshem, and E. Grushka. Anal. Chem. 52:1206–1209 (1980).

    Google Scholar 

  25. S. Lam, F. Chow, and A. Karmen. J. Chromatogr. 199:295–305 (1980).

    Google Scholar 

  26. L. R. Gelber, B. L. Karge, J. L. Neumeyer, and B. Feibush. J. Am. Chem. Soc. 106:7729–7734 (1984).

    Google Scholar 

  27. C. Pettersson, T. Arvidsson, A. L. Karlsson, and I. Marle. J. Pharm. Biomed. Anal. 4:221–235 (1986).

    Google Scholar 

  28. M. I. Popova and C. G. Kratchanov. J. Chromatogr. 72:192–197 (1972).

    Google Scholar 

  29. M. I. Popova, C. G. Kratchanov, and M. J. Kuntcheva. J. Chromatogr. 87:581–584 (1973).

    Google Scholar 

  30. L. Hackzell and G. Schill. Chromatographia 15:437–444 (1982).

    Google Scholar 

  31. D. Sybilska, J. Zukowski, and J. Bojarski. J. Liq. Chromatogr. 9:591 (1986).

    Google Scholar 

  32. D. Sybilska, J. Debowski, and J. Jurczak. J. Chromatgor. 237:303–306 (1982).

    Google Scholar 

  33. W. H. Pirkle, D. W. House, and J. M. Finn. J. Chromatogr. 192:143–158 (1980).

    Google Scholar 

  34. I. W. Wainer, T. D. Doyle, Z. Hamidazadeh, and M. Aldridge. J. Chromatogr. 268:106–109 (1983).

    Google Scholar 

  35. W. H. Pirkle, J. M. Finn, J. L. Schreiner, and B. C. Hamper. J. Am. Chem. Soc. 103:3964–3966 (1981).

    Google Scholar 

  36. N. Oi, M. Nagase, Y. Inda, and T. Doi. J. Chromatogr. 265:111–116 (1983).

    Google Scholar 

  37. A. Ichida, T. Shibata, I. Okamoto, Y. Yuki, H. Namikashi, and Y. Toga. Chromatographia 19:280–284 (1984).

    Google Scholar 

  38. I. W. Wainer and M. C. Alembik. J. Chromatogr. 358:85–93 (1986).

    Google Scholar 

  39. T. Shibata, I. Okamoto, and K. Ishii. J. Liq. Chromatogr. 9:313 (1986).

    Google Scholar 

  40. I. W. Wainer and T. D. Doyle. LC Mag. 2:88–94 (1984).

    Google Scholar 

  41. H. B. Weems and S. K. Young. Anal. Biochem. 125:156–161 (1982).

    Google Scholar 

  42. C. A. Demerson, L. G. Humber, N. A. Abraham, G. Schilling, R. R. Mantel, and C. Pace-Asciak. J. Med. Chem. 26:1778–1780 (1983).

    Google Scholar 

  43. Regis Chemical Co. Technical Bulletin (1986).

  44. I. W. Wainer, T. D. Doyle, K. H. Donn, and J. R. Powell. J. Chromatogr. 306:405–411 (1984).

    Google Scholar 

  45. I. W. Wainer, M. C. Alembik, and L. T. Fisher. Submitted for publication.

  46. M. C. Alembik and I. W. Wainer. J. Assoc. Offic. Anal. Chem. (in press).

  47. E. D. Lee, J. Henion, C. A. Brunner, and I. W. Wainer. Anal. Chem. 58:1349–1352 (1986).

    Google Scholar 

  48. I. W. Wainer. Chromatogr. Forum Dec.: 55–61 (1986).

  49. W. H. Pirkle and T. C. Pochapsy. J. Chromatogr. (in press).

  50. W. H. Pirkle and A. Tsipouras. J. Chromatogr. 291:291–298 (1984).

    Google Scholar 

  51. N. Widdenhof. Starke 21:164–169 (1969).

    Google Scholar 

  52. A. Harada, M. Fure, and S. A. Nozakura. J. Polymer. Sci. 16:189–196 (1978).

    Google Scholar 

  53. D. W. Armstrong. Patents pending, USA, Japan, Europe, 1984.

  54. M. L. Bender and M. Komiyama. Cyclodextrin Chemistry, Springer-Verlag, New York, 1978.

    Google Scholar 

  55. J. Szejtli. Cyclodextrins and Their Inclusion Complexes, Akademiai Kiado, Budapest, Hungary, 1982.

    Google Scholar 

  56. V. Daffe and J. Fastrez. J. Chem. Soc. Perkin Trans. 2:789–796 (1983).

    Google Scholar 

  57. M. Mikolajczyk and J. Drabowicz. J. Am. Chem. Soc. 100:2510–2515 (1978).

    Google Scholar 

  58. V. A. DaVanok, A. A. Kurganov, and A. S. Bochkov. In J. C. Giddings (ed.), Adv. Chromatogr., Vol. 22, J. B. Lippincott, Philadelphia, 1983 pp. 71–116.

    Google Scholar 

  59. D. W. Armstrong, T. J. Ward, R. D. Armstrong, and T. E. Beesley. Science 232:1132–1135 (1986).

    Google Scholar 

  60. T. E. Beesley. Am Lab. 17:78–83 (1985).

    Google Scholar 

  61. W. L. Hinze. Sep. Purif. Methods 10:159–237 (1981).

    Google Scholar 

  62. B. Feibush, M. Cohen, and B. L. Karger. J. Chromatogr. 282:3–26 (1983).

    Google Scholar 

  63. G. Blaschke, H. P. Kraft, K. Fickentscher, and F. Kohler. Arzneim.-forsch. 29:1640–1642 (1979).

    Google Scholar 

  64. B. G. Snider. J. Chromatogr. 341:548–553 (1986).

    Google Scholar 

  65. S. Allenmark, B. Bomgren, and H. Boren. J. Chromatogr. 269:63–68 (1983).

    Google Scholar 

  66. J. Hermansson. J. Chromatogr. 269:71–80 (1983).

    Google Scholar 

  67. G. Shill, I. W. Wainer, and S. Barkan. J. Liq Chromatogr 9:641–666 (1986).

    Google Scholar 

  68. J. Allenmark. Liq. Chromatogr 9:425 (1986).

    Google Scholar 

  69. A. H. Beckett. Prog. Drug Res. 1:455 (1959).

    Google Scholar 

  70. P. Jenner and B. Testa. Drug Metab. Res. 2:117 (1973).

    Google Scholar 

  71. I. W. Wainer, S. A. Barkan, and G. Schill. LC/GC Mag. 5:422–430 (1986).

    Google Scholar 

  72. J. Hermansson. J. Chromatogr. 325:379–384 (1985).

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacy and Pharmaceutics, Virginia Commonwealth University, Box 581 MCV Station, Richmond, Virginia, 23298-0001

    H. Thomas Karnes

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  1. H. Thomas Karnes
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  2. Mohamadi A. Sarkar
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Karnes, H.T., Sarkar, M.A. Enantiomeric Resolution of Drug Compounds by Liquid Chromatography. Pharm Res 4, 285–292 (1987). https://doi.org/10.1023/A:1016437018323

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