Chromatographia

, Volume 39, Issue 5–6, pp 355–362 | Cite as

Ruggedness testing of gas chromatographic method for residual solvents in pharmaceutical substances

  • G. Wynia
  • P. Post
  • J. Broersen
  • F. A. Maris
Originals

Summary

Ruggedness testing is performed on a gas chromatographic method for the quantitative determination of residual solvents in steroids. Eight experimental variables or factors which were expected to influence the quantitative results were selected. These factors were divided into two independent groups, i.e. four factors related to the injection process and four factors related to separation and detection. In order to determine interaction between factors and quadratic effects, a central composite design was selected for the set-up of the experiments. Because in the method an internal standard is used, relative peak area was used as response. A deviation of up to 2.5% per factor for the quantitative results was regarded as acceptable. Other responses studied are related to the system suitability. Observed main, quadratic and interaction effects were translated into rugged intervals of the experimental variables by graphical presentation. It was found that besides main effects significant interaction effects were present, for example between the temperature of the injector and the split-flow. Interaction effects can easily result in the reduction of the rugged intervals by a factor of 2. The calculated rugged intervals were compared with the precision of the instrument or factor settings in order to estimate the ruggedness of the factors. Eventually, the maximum effect of the variation in the instrument settings on the quantitative results regarding the precision of the factor settings was found to be only 2.2%. Overall, the method proved to be rugged for most factors, except for the split-flow of the injector for which the method was only rugged to a limited extent.

Key Words

Gas chromatography Method validation Reggedness test Residual solvents 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    W. Larry Paul, Pharmaceutical Technology, 130 (3–1991).Google Scholar
  2. [2]
    M. Mulholland, Trends in Analytical Chemistry7, 383 (1988).Google Scholar
  3. [3]
    K. Jorgensen, L. Jacobsen, International Journal of Pharmaceutics,88, 23 (1992).Google Scholar
  4. [4]
    M. Mulholland, J. Waterhouse, Journal of Chromatographics395, 593 (1987).Google Scholar
  5. [5]
    M. Mulholland, P. J. Naish, D. R. Stout, Chemometrics and Intelligent Laboratory Systems5, 263 (1989).Google Scholar
  6. [6]
    P. Kane, N. Rothmann, LC-GC,11, 813 (1993).Google Scholar
  7. [7]
    M. Mulholland, J. Waterhouse, Chromatographia25, 769 (1988).Google Scholar
  8. [8]
    S. N. Deming, S. L. Morgan, Experimental Design: A Chemometric Approach (Data handling in Science and Technology, Vol. 3), Elsevier Amsterdam 1987, ch. 11, p. 181.Google Scholar
  9. [9]
    R. L. Plackett, J. P. Burman, Biometrika33, 305 (1946).Google Scholar
  10. [10]
    G. E. P. Box, W. G. Hunter, J. G. Stuart Hunter, Statistics for experiments, An Introduction to Design Data Analysis and Model building. Whiley, New York 1978, Part III ch. 9–13, p. 29.Google Scholar
  11. [11]
    Y. van der Heyden, M. S. Khots, D. L. Massart, Analytica Chemica Acta276, 189 (1993).Google Scholar
  12. [12]
    L. Buydens, P. J. Schoenmakers, F. Maris, H. Hindriks, Analytica Chimica Acta272, 419 (1993).Google Scholar
  13. [13]
    J. H. de Boer, A. K. Smilde, D. A. Doornbos, Chemometrics and Intelligent Laboratory Systems,15, 13 (1991).Google Scholar
  14. [14]
    J. A. van Leeuwen, L. M. C. Buydens, B. G. M. Vandeginste, G. Kateman, P. J. Schoenmakers, M. Mulholland, Chemometrics and Intelligent Laboratory Systems,10, 337 (1991).Google Scholar
  15. [15]
    J. A. van Leeuwen, L. M. C. Buydens, B. G. M. Vandeginste, G. Kateman, P. J. Schoenmakers, M. Mulholland, Chemometrics and Intelligent Laboratory Systems,11, 37 (1991).Google Scholar
  16. [16]
    J. A. van Leeuwen, L. M. C. Buydens, B. G. M. Vandeginste, G. Kateman, A. Cleland, M. Mulholland, C. Jansen, F. A. Maris, P. H. Hoogkamer, J. H. M. van den Berg, Chemometrics and Intelligent Laboratory Systems,11, 161 (1991).Google Scholar
  17. [17]
    E. Morgan, K. W. Burton, P. A. Church, Chemometrics and Intelligent Laboratory Systems,5, 238 (1989).Google Scholar
  18. [18]
    G. E. P. Box, D. W. Behnken, Technometrics2, 455 (1960).Google Scholar
  19. [19]
    I. D. Smith, D. G. Waters, Analyst,116, 1327 (1991).Google Scholar

Copyright information

© Friedr. Vieweg & Sohn Verlagsgesellschaft mbH 1994

Authors and Affiliations

  • G. Wynia
    • 1
  • P. Post
    • 1
  • J. Broersen
    • 1
  • F. A. Maris
    • 1
  1. 1.Quality Assurance DepartmentN.V. OrganonOssThe Netherlands

Personalised recommendations