Skip to main content
SpringerLink
Log in

Aspects of the chemical stability of doxorubicin and seven other anthracydines in acidic solution

  • Original Articles
  • Published:
Pharmaceutisch Weekblad Aims and scope Submit manuscript

Abstract

The degradation of doxorubicin in acidic medium has been investigated using a stability indicating high pressure liquid chromatographic assay. Influences of temperature, pH and ionic strength on the degradation rate are quantified. The stability of doxorubicin at 50°C is compared with those of seven related anthracyclines. The aglycone degradation products are characterized by mass spectrometry and by chromatography.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Davis HL, Davis TE. Daunorubicin and adriamycin in cancer treatment: An analysis of their roles and limitations. Cancer Treat Rep 1979;63:809–15.

    PubMed  Google Scholar 

  2. Crooke ST, Reich SD. Anthracyclines: current status and new developments. New York: Academic Press, 1980.

    Google Scholar 

  3. Carter SK. Adriamycin — A review. J Natl Cancer Inst 1975;55:1265–73.

    PubMed  Google Scholar 

  4. Barbieri B, Bellini O, Savi G, Bertazolli C, Penco S, Casazza AM. Antitumour activity and cardiotoxicity of new 4-demethoxyanalogues of daunorubicin and doxorubicin. Drugs Exptl Clin Res 1984;10:85–90.

    Google Scholar 

  5. Formelli F, Casazza AM. Biological and pharmacological properties of new anthracycline derivatives. Drugs Exptl Clin Res 1984;10:75–84.

    Google Scholar 

  6. Harper H, Kemeny N, Cheng E, Sordillo P, Ahmed T. Phase II trial of 4-demethoxydaunorubicin (DMDR) in advanced colorectal carcinoma. Proc Am Assoc Cancer Res 1983;24:148.

    Google Scholar 

  7. Ferrari L, Rossi A, Brambilla C, et al. Phase I study with 4′-deoxydoxorubicin. Proc Am Assoc Cancer Res 1983;24:163.

    Google Scholar 

  8. Arcamone F, Franceschi G, Penco S. Adriamycin (14-hydroxydaunomycin), a novel antitumor antibiotic. Tetrahedron Letters 1969;13:1007–10.

    Article  PubMed  Google Scholar 

  9. Wassermann K, Bundgaard H. Kinetics of the acidcatalyzed hydrolysis of doxorubicin. Int J Pharm 1983;14:73–8.

    Article  Google Scholar 

  10. Tavoloni N, Guarino AM, Berk PD. Photolytic degradation of adriamycin. J Pharm Pharmacol 1980;32: 860–2.

    PubMed  Google Scholar 

  11. Daugherty JP, Hixon SC. Photolytic destruction of adriamycin. J Pharm Pharmacol 1981;33:556.

    PubMed  Google Scholar 

  12. Thoma K, Strittmatter T, Steinbach D. Untersuchungen zur Photoinstabilität von Antibiotika. Acta Pharm Techn 1980;26:269–72.

    Google Scholar 

  13. Williams BA, Tritton TR. Photoinactivation of anthracyclines. Photochem Photobiol 1981;34:131–4.

    Google Scholar 

  14. Karlsen J, Thønessen HH, Olsen IR, Sollien AH, Skobba TJ. Stability of cytotoxic intravenous solutions subjected to freeze-thaw treatment. Nor Pharm Acta 1983;45:61–7.

    Google Scholar 

  15. Benvenuto JA, Anderson RW, Kerkof K, Smith RG, Loo TL. Stability and compatibility of antitumor agents in glass and plastic containers. Am J Hosp Pharm 1981;38:1914–8.

    PubMed  Google Scholar 

  16. Hoffman DM, Grossano DD, Damin LA, Woodcock TM. Stability of refrigerated and frozen solutions of doxorubicin hydrochloride. Am J Hosp Pharm 1979;36:1536–8.

    PubMed  Google Scholar 

  17. Poochikian GK, Cradock JC, Flora KP. Stability of anthracycline antitumor agents in four infusion fluids. Am J Hosp Pharm 1981;38:483–6.

    PubMed  Google Scholar 

  18. Ketchum D, Wolf E, Sesin GP. Cost benefit and stability study of doxorubicin following reconstitution. Am J Intrav Ther Clin Nutr 1981:15–8.

  19. Eksborg S, Ehrsson H, Wallin I, Lindfors A. Quantitative determination of adriamycin and daunorubicinhandling of blood and plasma samples. Acta Pharm Suec 1981;18:215–20.

    PubMed  Google Scholar 

  20. Schwartz HS, Paul B. Biotransformations of daunorubicin aglycones by rat liver microsomes. Cancer Res 1984;44:2480–4.

    PubMed  Google Scholar 

  21. Schwartz HS, Parker NB. Initial biotransformations of daunorubicin to aglycones by rat liver microsomes. Cancer Res 1981;41:2343–8.

    PubMed  Google Scholar 

  22. Bates RG. Determination of pH theory and practice. 2nd ed. New-York-London-Sydney-Toronto: John Wiley & Sons, 1973.

    Google Scholar 

  23. Tomlinson E, Malspeis L. Concomitant adsorption and stability of some anthracycline antibiotics. J Pharm Sci 1982;71:1121–5.

    PubMed  Google Scholar 

  24. Aszalos A. Analysis of antitumor antibiotics by high pressure liquid chromatography (HPLC). J Liq Chromatogr 1984;7(S-1):69–125.

    Google Scholar 

  25. Sturgeon RJ, Schulman SG. Electronic absorption spectra and protolytic equilibria of doxorubicin: direct spectrophotometric determination of microconstants. J Pharm Sci 1977;6:958–61.

    Google Scholar 

  26. Arcamone F, Franceschi G, Orezzi P, Cassinelli G, Barbieri W, Mondelli R. Daunomycin. I. The structure of daunomycinone. J Am Chem Soc 1904;86:5334–5.

    Article  Google Scholar 

  27. Gioia B, Arlandini E, Vigevani A. Field desorption mass spectrometry of anthracyclines. Comparison with other soft ionization techniques. Biomed Mass Spectrom 1984;11:35–40.

    Article  Google Scholar 

  28. Roller PP, Sutphin M, Aszalos AA. Mass spectrometry of N-acylated daunorubicin derivatives. Biomed Mass Spectrom 1976;3:166–71.

    Article  PubMed  Google Scholar 

  29. Watson E, Chan KK. GLC-Mass spectrometry of several important anticancer drugs I: Pertrimethylsilylation andO-methoxime formation. J Pharm Sci 1978;67:1243–6.

    PubMed  Google Scholar 

  30. Vigevani A, Gioia B, Cassinelli G. Mass spectrometry of some N-acyldaunosamine derivatives. Carbohydr Res 1974;32:321–30.

    Article  PubMed  Google Scholar 

  31. Smith RG. Characterization of anthracycline antibiotics by desorption chemical ionization mass spectrometry. Anal Chem 1982;54:2006–8.

    Article  Google Scholar 

  32. Menozzi M, Valentini L, Vannini E, Arcamone F. Self-association of doxorubicin and related compounds in aqueous solution. J Pharm Sci 1984;73:766–70.

    PubMed  Google Scholar 

  33. Chaires JB, Dattagupta N, Crothers DM. Self-association of daunomycin. Biochemistry 1982;21:3927–32.

    Article  PubMed  Google Scholar 

  34. Miyamoto E, Odashima S, Kitagawa I, Tsuji A. Stability kinetics of ginsenosides in aqueous solution. J Pharm Sci 1984;73:409–10.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Analytical Pharmacy, Subfaculty of Pharmacy, State University of Utrecht, Catharijnesingel 60, 3511, GH Utrecht, The Netherlands

    J. H. Beijnen, G. Wiese & W. J. M. Underberg

Authors
  1. J. H. Beijnen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Wiese
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. J. M. Underberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beijnen, J.H., Wiese, G. & Underberg, W.J.M. Aspects of the chemical stability of doxorubicin and seven other anthracydines in acidic solution. Pharmaceutisch Weekblad Scientific Edition 7, 109–116 (1985). https://doi.org/10.1007/BF01968712

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01968712

Keywords

Search

Navigation