, Volume 44, Issue 7–8, pp 355–361 | Cite as

Improvements in drug purity determination by capillary electrophoresis using UV-absorption and LIF-detection with a UV-laser

  • O. Stålberg
  • D. Westerlund
  • U-K. Hultin
  • S. Schmidt


In drug purity determinations by capillary electrophoresis using UV-detection generally a relative high concentration of the main compound has to be injected. Principles how to handle overloading effects are described. NXX-066 is a drug with a native fluorescence which made it possible to use of CE system equipped with a LIF-detection unit. Monitoring drug purity determination with LIF detection results in an improved limit of quantification of the impurities and/or opens a possibility to avoid an overloaded main peak. A frequency doubled (FRED) argon ion laser set at 244 nm was used as excitation source in drug purity determination with the LIF-detection unit and the chemicals used were therefore carefully chosen in order to minimize the background noise level, which easily is enhanced when fluorescence detection is performed in the UV-range. The separation of the fluorescent NXX-066 analogues proved to be a difficult task, but an adequate resolution was obtained when β- and γ-cyclodextrins was added as structural selectors and the separation window was expanded by the use of a repressed/reversed electroosmotic flow. A comparison of the separation capability for the UV-detection system and the laser induced fluorescence detection system was performed, showing that the overloading effects of the main peak can be removed using the CE-LIF system and thereby obtain a substantially improved resolution of the analogues. A comparison of LC-UV and CE-UV for drug purity determination of a crude product from, synthesis of NXX-066 is also included in this paper where a good correlation of the results were obtained.

Key Words

Capillary electrophoresis Drug purity Frequency doubled laser Laser induced fluorescence Reduced electromigration dispersion 


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  1. [1]
    K. D. Altria, J. Chromatogr.646, 245 (1993).CrossRefGoogle Scholar
  2. [2]
    K. D. Altria, Chromatographia35, 493 (1993).CrossRefGoogle Scholar
  3. [3]
    S. Folestad, L. Johnsson, B. Josefsson, B. Galle, Anal. Chem.54, 925 (1982).Google Scholar
  4. [4]
    E. S. Yeung, P. Wang, W. Li, R. W. Giese, J. Cromatogr.608, 73 (1992).CrossRefGoogle Scholar
  5. [5]
    H. E. Schwartz, K. J. Ulfelder, Anal. Chem.64, 1737 (1992).CrossRefGoogle Scholar
  6. [6]
    M. C. Ruiz-Martinez, J. Berka, A. Belenkii, F. Foret, A. W. Miller, B. L. Karger, Anal. Chem.65, 2851 (1993).CrossRefGoogle Scholar
  7. [7]
    K. Srinivasan, J. E. Girard, P. Williams, R. K. Roby, V. W. Weedn, S. C. Morris, M. C. Kline, D. J. Reeder, J. Chromatogr.652, 83 (1993).CrossRefGoogle Scholar
  8. [8]
    E. F. Rossomando, L. White, K. J. Ulfelder, J. Chromatogr.656, 159 (1993).Google Scholar
  9. [9]
    T. Manabe, N. Chen, S. Terabe, M. Yohda, I. Endo, Anal. Chem.66, 4243 (1994).CrossRefGoogle Scholar
  10. [10]
    H. Arakawa, K. Uetanaka, M. Maeda, A. Tsuji, Y. Matsubara, K. Narisawa, J. Chromatogr.656, 517 (1994).CrossRefGoogle Scholar
  11. [11]
    T. T. Lee, S. J. Lillard, E. S. Yeung, Electrophoresis,14, 429 (1993).CrossRefGoogle Scholar
  12. [12]
    N. J. Reinhoud, U. R. Tjaden, J. van der Greef, J. Chromatogr.673, 255 (1994).CrossRefGoogle Scholar
  13. [13]
    N. J. Reinhoud, U. R. Tjaden, J. van der Greef, J. Chromatogr.574, 327 (1992).Google Scholar
  14. [14]
    T. T. Lee, E. S. Yeung, Anal. Chem.64, 3045 (1992).CrossRefGoogle Scholar
  15. [15]
    K. J. Miller, F. E. Lytle, J. Chromatogr.648, 245 (1993).CrossRefGoogle Scholar
  16. [16]
    J. Bergquist, S. D. Gilman, A. G. Ewing, R. Ekman, Anal. Chem.66, 3512 (1994).CrossRefGoogle Scholar
  17. [17]
    O-W. Werner, R. Lausch, T. Scheper, R. Freitag, Anal. Chem.66, 4027 (1994).CrossRefGoogle Scholar
  18. [18]
    F-T. A. Chen, J. C. Sternberg, Electrophoresis,14, 13 (1994).CrossRefGoogle Scholar
  19. [19]
    F-T. A. Chen, S. L. Pentoney, Jr., J. Chromatogr.680, 425 (1994).CrossRefGoogle Scholar
  20. [20]
    H. Soini, M. V. Novotny, M-L. Riekkola, J. Microcol. Sep.4, 313 (1992).CrossRefGoogle Scholar
  21. [21]
    E. Gonzalez, R. Montes, J. J. Laserna, Anal. Chim. Acta282, 687 (1993).CrossRefGoogle Scholar
  22. [22]
    N. Wu, B. Li, J. V. Sweedler, J. Liq. Chromatogr.17, 1917 (1994).Google Scholar
  23. [23]
    O. Stålberg, D. Westerlund, U-B. Rodby, S. Schmidt, Chromatographia41, 697 (1995).CrossRefGoogle Scholar
  24. [24]
    T. T. Lee, E. S. Yeung, J. Chromatogr.595, 319 (1992).CrossRefGoogle Scholar
  25. [25]
    J. A. Taylor, E. S. Yeung, Anal. Chem.64, 1741 (1992).CrossRefGoogle Scholar
  26. [26]
    X. C. Huang, M. A. Quesada, R. A. Mathies, Anal. Chem.64, 967 (1992).CrossRefGoogle Scholar
  27. [27]
    R. E. Milofsky, E. S. Yeung, Anal. Chem.65, 153 (1993).CrossRefGoogle Scholar
  28. [28]
    J. A. Taylor, E. S. Yeung, Anal. Chem.65, 956 (1993).CrossRefGoogle Scholar
  29. [29]
    S. Nie, R. Dadoo, R. N. Zare, Anal. Chem.65, 3571 (1993).CrossRefGoogle Scholar
  30. [30]
    M. Jansson, J. Roerade, F. Laurell, Anal. Chem.65, 2766 (1993).CrossRefGoogle Scholar
  31. [31]
    K. C. Chan, G. M. Janini, G. M. Muschik, H. J. Issaq, J. Liq. chromatogr.16, 1877 (1994).Google Scholar
  32. [32]
    S. R. Rabel, R. Trueworthy, J. F. Stobaugh, J. High Resol Chrom. 16,326 (1993).Google Scholar
  33. [33]
    T. Higashijima, T. Fuchigami, T. Imasaka, N. Ishibashi, Anal. Chem.64, 711 (1992).CrossRefGoogle Scholar
  34. [34]
    T. Fuchigami, T. Imasaka, M. Shiga, Anal. Chim. Acta282, 209 (1993).CrossRefGoogle Scholar
  35. [35]
    F-T. A. Chen, A. Tusak, S. Pentoney Jr. K. Konrad, C. Lew, E. Koh, J. Sternberg, J. Chromatogr.652, 355 (1993).CrossRefGoogle Scholar
  36. [36]
    T. Okazaki, T. Imasaka, N. Ishibashi, Anal. Chim. Acta209, 327 (1988).CrossRefGoogle Scholar
  37. [37]
    J. Webjörn, F. Laurell, G. Arvidsson, J. Lightw, Techn.7, 1597 (1989).Google Scholar
  38. [38]
    J. D. Bierlein, H. Vanherzeele, J. Opt. Soc. Am.6, 622 (1989).CrossRefGoogle Scholar
  39. [39]
    J. B. Shear, L. A. Colón, R. N. Zare, Anal. Chem.65, 3708 (1992).CrossRefGoogle Scholar
  40. [40]
    J. B. Shear, R. Dadoo, H. A. Fishman, R. H. Scheller, R. N. Zare, Anal. Chem.65, 1741 (1993).Google Scholar
  41. [41]
    E. Arriaga, D. Y. Chen, X. L. Cheng, N. J. Dovichi, J. Chromatogr.652, 347 (1993).CrossRefGoogle Scholar
  42. [42]
    B. Krattiger, A. E. Bruno, H. M. Widmer, R. Dändiger, Anal. Chem.67, 124 (1995).CrossRefGoogle Scholar
  43. [43]
    R. L. Williams, G. Vigh, J. Chromatogr.730, 273 (1996).CrossRefGoogle Scholar
  44. [44]
    O. Stålberg, H. Brötell, D. Westerlund, Chromatographia,40, 697 (1995).CrossRefGoogle Scholar
  45. [45]
    O. Stålberg, J. Ståhlberg, J. Chromatogr. (in press).Google Scholar
  46. [46]
    S. Hjertén, Electtrophoresis11, 665 (1990).CrossRefGoogle Scholar
  47. [47]
    R. L. Williams, G. Vigh, J. Liq. Chrom.18, 3813 (1995).Google Scholar
  48. [48]
    J. C. Giddings, Sep. Sci.4, 181 (1969).Google Scholar

Copyright information

© Friedr. Vieweg & Sohn Verlagsgesellschaft mbH 1997

Authors and Affiliations

  • O. Stålberg
    • 1
  • D. Westerlund
    • 1
  • U-K. Hultin
    • 2
  • S. Schmidt
    • 2
  1. 1.Analytical Pharmaceutical ChemistryUppsala University Biomedical CentreUppsalaSweden
  2. 2.Astra Arcus AB, Analytical and Pharmaceutical R & DSödertäljeSweden

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