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Predictive analytical workflow for rapid structure elucidation and in silico toxicological qualification of an unidentified impurity in cefixime granules for oral suspension Cover

Predictive analytical workflow for rapid structure elucidation and in silico toxicological qualification of an unidentified impurity in cefixime granules for oral suspension

Open Access
|Mar 2026

References

  1. R. N. Brogden and D. M. Richards, Cefixime: A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential, Drugs 38(4) (1989) 524–550; https://doi.org/10.2165/00003495-198938040-00004
  2. S. C. Sweetman (Ed.), Martindale: The Complete Drug Reference, 33rd ed., Pharmaceutical Press, London 2002.
  3. T. I. Lucas, R. H. Bishara and R. H. Seevers, A stability program for the distribution of drug products, Pharm. Technol. 28(7) (2004) 68–73.
  4. European Medicines Agency, Note for guidance on in-use stability testing of human medicinal products, CPMP/QWP/2934/99, EMA, London 2001.
  5. S. Kitamura, A. Miyamae, S. Koda and Y. Morimoto, Effect of grinding on the solid-state stability of cefixime trihydrate, Int. J. Pharm. 56(2) (1989) 125–134; https://doi.org/10.1016/0378-5173(89)90005-7
  6. S. Kitamura, S. Koda, A. Miyamae, T. Yasuda and Y. Morimoto, Dehydration effect on the stability of cefixime trihydrate, Int. J. Pharm. 59(3) (1990) 217–224; https://doi.org/10.1016/0378-5173(90)90112-H
  7. International Conference on Harmonisation, Impurities in new drug products Q3B(R2), ICH Harmo nised Tripartite Guideline, Step 4, Geneva 2006.
  8. European Medicines Agency, Guideline on setting specifications for related impurities in antibiotics, EMA/CHMP/CVMP/QWP/199250/2009 corr., EMA, London 2012.
  9. R. Benigni, C. Bossa, N. Jeliazkova, T. Netzeva and A. Worth, The Benigni/Bossa rulebase for mutagenicity and carcinogenicity, EUR 24895 EN, Publications Office of the European Union, Luxembourg 2011.
  10. R. Benigni, C. Bossa and O. Tcheremenskaia, In vitro cell transformation assays for an integrated assessment of carcinogenicity, Mutagenesis 28(1) (2013) 107–116; https://doi.org/10.1093/mutage/ges050
  11. R. Benigni, C. Bossa, O. Tcheremenskaia and A. Worth, Development of structural alerts for the in vivo micronucleus assay in rodents, EUR 23981 EN, Publications Office of the European Union, Luxembourg 2009.
  12. R. Benigni and C. Bossa, Mechanisms of chemical carcinogenicity and mutagenicity: Implications for predictive toxicology, Chem. Rev. 111(4) (2011) 2507–2536; https://doi.org/10.1021/cr100222q
  13. United States Environmental Protection Agency, Toxicity Estimation Software Tool (TEST), EPA, Washington (DC) 2015.
  14. United States Environmental Protection Agency, User’s Guide for T.E.S.T., EPA, Washington (DC) 2012.
  15. T. M. Martin, P. Harten, R. Venkatapathy, S. Das and D. M. Young, A hierarchical clustering metho dology for toxicity estimation, Toxicol. Mech. Methods 18(2–3) (2008) 251–266; https://doi.org/10.1080/15376510701857395
  16. QSAR Toolbox, Version 3.3, OECD, Paris; http://www.qsartoolbox.org
  17. A. Sutter, A. Amberg, S. Boyer, A. Brigo, J. F., Contrera, L. L. Custer, K. L. Dobo, V. Gervais, S. Glowienke, J. van Gompel, N. Greene, W. Muster, J. Nicolette, M. Vijayaraj Reddy, V. Thybaud, E. Vock, A. T. White and L. Müller, Use of in silico systems and expert knowledge for structure-based assessment of potentially mutagenic impurities, Regul. Toxicol. Pharmacol. 67(1) (2013) 39–52; https://doi.org/10.1016/j.yrtph.2013.05.001
  18. J. F. Contrera, Validation of Toxtree and SciQSAR predictive software, Regul. Toxicol. Pharmacol. 67(2) (2013) 285–293; https://doi.org/10.1016/j.yrtph.2013.08.012
  19. S. M. Pawar and S. R. Dhaneshwar, Stability-indicating HPTLC method for desvenlafaxine, J. Liq. Chromatogr. Relat. Technol. 35(4) (2012) 449–510; https://doi.org/10.1080/10826076.2011.601500
  20. D. Saini, S. Baboota, M. Ali, H. Patel, P. Jain, S. Neerumulla and J. Ali, Stability-indicating UPLC method for raloxifene hydrochloride, J. Liq. Chromatogr. Relat. Technol. 35(2) (2012) 162–173; https://doi.org/10.1080/10826076.2011.597067
  21. K. M. Al Azzam, B. Saad, A. Makahleah, H. Y. Aboul-Enein and A. A. Elbashir, MEKC assay for valacyclovir and impurities, Biomed. Chromatogr. 24(5) (2010) 535–543; https://doi.org/10.1002/bmc.1323
  22. R. Sehrawat, M. Maithani and R. Singh, Regulatory aspects of stability-indicating methods, Chroma tographia 72(1–2) (2010) 1–6; https://doi.org/10.1365/s10337-010-1612-z
  23. Z. Talebpour, H. Pourabdollahi, H. Rafati, A. Abdollahpour, Y. Bashour and H. Y. Aboul-Enein, Determination of cefixime by a validated stability-indicating HPLC method and identification of its related substances by LC-MS/MS studies, Sci. Pharm. 81(2) (2013) 493–503; https://doi.org/10.3797/scipharm.1301-15
  24. E. H. K. Adam, A. E. M. Saeed and I. E. Barakat, Degradation of cefixime trihydrate under stress conditions, Der Pharma Chem. 3(6) (2011) 197–207.
  25. Y. Namiki, T. Tanabe, T. Kobayashi, J. Tanabe, Y. Okimura, S. Koda and Y. Morimoto, Degradation kinetics and mechanisms of a new cephalosporin, cefixime, in aqueous solution, J. Pharm. Sci. 76(3) (1987) 208–214; https://doi.org/10.1002/jps.2600760305
  26. H. Wang, H. Huang, J. Cao, D. Chui and S. Xiao, Mass spectral differentiation of b-lactams, Biomed. Res. Int. 2015 (2015) Article ID 697958 (13 pages); https://doi.org/10.1155/2015/697958
  27. A. D. Deshpande, K. G. Baheti and N. R. Chatterjee, Degradation of b-lactam antibiotics, Curr. Sci. 87(12) (2004) 1684–1695.
  28. D. Wang and R. E. Notari, Cefuroxime hydrolysis kinetics in aqueous solution, J. Pharm. Sci. 83(4) (1994) 577–581; https://doi.org/10.1002/jps.2600830420
  29. A. Uzunović, E. Vranić and J. Hadžiabdić, Stability of cefuroxime axetil oral suspension, Bosn. J. Basic Med. Sci. 8(1) (2008) 93–96; https://doi.org/10.17305/bjbms.2008.3005
DOI: https://doi.org/10.2478/acph-2026-0005 | Journal eISSN: 1846-9558 | Journal ISSN: 1330-0075
Language: English
Page range: 1 - 25
Accepted on: Dec 29, 2025
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Published on: Mar 25, 2026
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
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© 2026 Ivana Mitrevska, Marina Chachorovska, Gjorgji Petrushevski, published by Croatian Pharmaceutical Society
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.