Pharmaceutical Chemistry Journal

, Volume 53, Issue 5, pp 477–482 | Cite as

Correction Factors in Formulas for Calculating Impurity Contents: Essence and Determination Methods and Their Limitations

  • N. A. ÉpshteinEmail author

Formulas for calculating relative response factors (RRFs) and correction factors (Fs) of impurities and those necessary for understanding the essence of RRFs and Fs are presented. The main methods for determining Fs and their limitations (conditions necessary for correct determination of RRFs and Fs) are considered. These limitations do not appear in the European and US pharmacopoeias although they must be considered to determine the correct Fs. Examples and recommendations are given for reliable determination and correct use of the Fs.


correction factor response factor relative response factor impurities recommendations 


  1. 1.
    L. Bhattacharyya, H. Pappa, K. A. Russo, et al., Pharmacopeial Forum, 31(3), 2 – 8 (2005).Google Scholar
  2. 2.
    J. Ermer and J. H. McB. Miller, Method Validation in Pharmaceutical Analysis: A Guide to Best Practice, Wiley-VCH, Weinheim, 2005 [Russian translation, VIALEK, Moscow, 2013].Google Scholar
  3. 3.
    H.-J. Kuss and S. Kromidas (eds.), Quantification in LC and GC. A Practical Guide to Good Chromatographic Data, Wiley-VCH Verlag GmbH & Co., KGaA, Weinheim, 2009, p. 221.Google Scholar
  4. 4.
    Technical Guide for the Elaboration of Monographs, EDQM, European Pharmacopoeia, 2015, pp. 25 – 26, 32.Google Scholar
  5. 5.
    European Pharmacopoeia, 9th Ed., Chap. 2.2.46, Chromatographic Separation Techniques, 2017.Google Scholar
  6. 6.
    L. R. Snyder, J. J. Kirkland., and J. L. Glajch, Practical HPLC Method Development, J. Wiley, New Jersey, 2010, p. 521.Google Scholar
  7. 7.
    The United States Pharmacopoeia, Chromatography, USP39-NF34, 2016.Google Scholar
  8. 8.
    K. Sasaki, T. Oki, T. Kobayashi, et al., Biosci., Biotechnol. Biochem., 78(12), 2073 – 2080 (2014).CrossRefGoogle Scholar
  9. 9.
    V. M. Peshkova and M. I. Gromova, Absorption Spectroscopy Methods in Analytical Chemistry [in Russian], I. P. Alimarina (ed.), Vysshaya Shkola, Moscow, 1976.Google Scholar
  10. 10.
    V. K. Chakravarthy, G. K. Babu, R. L. Dasu, et al., Rasayan J. Chem., 4(4), 919 – 943 (2011).Google Scholar
  11. 11.
    N. A. Épshtein, Vedom. NTsESMP, 7(2), 85 – 91 (2017).Google Scholar
  12. 12.
    Validation of Analytical Procedures, Establishment (Handling and Characterization) of Reference Standards in the Testing of Medical Products, B. A. H., Bonn, 2009, p. 76.Google Scholar
  13. 13.
    K. Doerffel, Statistik in der analytischen Chemie, Deutscher Verlag fur Grundstoffindustrie, Leipzig, 1990 [Russian translation, Mir, Moscow, 1994, p. 177].Google Scholar
  14. 14.
    International Conference on Harmonization (ICH), Harmonised Tripartite Guideline, ICH Q2(R1), Validation of Analytical Procedures: Text and Methodology, Geneva, 2005.Google Scholar
  15. 15.
    Y. Zhou, Y. Guan, J. Shi, et al., Chem. Cent. J., 6:150, 1 – 11 (2012).Google Scholar
  16. 16.
    M. A. Nussbaum, S. W. Baertschi, and P. J. Jansen, J. Pharm. Biomed. Anal., 27(6), 983 – 993 (2002).CrossRefGoogle Scholar
  17. 17.
    A. Koelewijn, The Applicability of Universal Detection in the Pharmaceutical Industry, University of Amsterdam, Amsterdam, 2014.Google Scholar
  18. 18.
    X. Liang, H. Patel, J. Young, et al., J. Pharm. Biomed. Anal., 47(4 – 5), 723 – 730 (2008).CrossRefGoogle Scholar
  19. 19.
    N. A. Épshtein, Razrab. Regist. Lek. Sredstv, 3(16), 54 – 68 (2016).Google Scholar
  20. 20.
    Waters 2998 Photodiode Array Detector Operator’s Guide, Waters Corp., 2010.dGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Center for Registration and Development of Medicines, LLC IRVIN 2MoscowRussia

Personalised recommendations