Advertisement

Pharmacy World and Science

, Volume 15, Issue 3, pp 123–127 | Cite as

Kinetics and mechanism of the degradation of la-acetylmitomycin C in aqueous solution

  • W. J. M. Underberg
  • J. H. Beijnen
Articles
  • 66 Downloads

Abstract

The acid-catalyzed degradation of mitomycin C is supposed to be governed, to a certain extent, by the protonation status of the aziridine nitrogen in the molecule as well as the protonation degree of the opened aziridine function in a key intermediate species, formed during mitomycin degradation. In order to obtain information about the contribution of the protonation degrees of these functions in controlling the degradation processes, we investigated the degradation of 1a-acetylmitomycin C in acidic aqueous solutions. In the presence of 0.001 mol/l phosphate buffers five 1-hydroxy and mono-acetyl mitosenes are formed, whereas in 1.0 mol/l acetate buffers a total of eight products could be identified, two of them being diacetyl mitosenes. Over the whole pH range studied the formation of 1,2-Z-mitosenes prevails, indicating that, contrary tomitomycin C, a pH-independent factor controls the ultimate 1,2-stereochemistry.

Keywords

Catalysis Drug stability Mitomycins Reaction kinetics Reaction mechanisms Stereoisomers 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Lown JW, Begleiter A, Johnson D, Morgan R. Studies related to antitumor antibiotics V. Reaction of mitomycin C with DNA examined by ethidium fluorescence assay. Can J Biochem 1976;54:110–9.PubMedGoogle Scholar
  2. 2.
    Lown JW, Weir G. Studies related to antitumor antibiotics. Part XIV. Reactions of mitomycin B with DNA. Can J Biochem 1978;56:296–304.Google Scholar
  3. 3.
    Tomasz M, Lipman R, Verdine GL, Nakanishi K. Nature of the destruction of deoxyguanosine residues by mitomycin C activated by mild acid pH. J Am Chem Soc 1985;107:6120–1.Google Scholar
  4. 4.
    Beijnen JH, Van der Houwen OAGJ, Rosing H, Underberg WJM. A systematic study on the chemical stability of mitomycin A and mitomycin B. Chem Pharm Bull 1986;34: 2900–13.PubMedGoogle Scholar
  5. 5.
    Beijnen JH, Underberg WJM. Degradation of mitomycin C in acidic solution. Int J Pharm 1985;24:219–29.Google Scholar
  6. 6.
    Beijnen JH, Lingeman H, Van Munster HA, Underberg WJM. Mitomycin antitumour agents: a review of their physicochemical and analytical properties and stability. J Pharm Biomed Anal 1986;4:275–95.Google Scholar
  7. 7.
    Beijnen JH, Fokkens RH, Rosing H, Underberg WJM. Degradation of mitomycin C in acid phosphate and acetate buffer solutions. Int J Pharm 1986;32:111–21.Google Scholar
  8. 8.
    Stevens CL, Taylor KG, Munk ME, Marshall WS, Noll K, Shah GD, et al. Chemistry and structure of mitomycin C. J Med Chem 1963;8:1–10.Google Scholar
  9. 9.
    Underberg WJM, Lingeman H. Aspects of the chemical stability of mitomycin and porfiromycin in acidic solution. J Pharm Sci 1983;72:549–53.PubMedGoogle Scholar

Copyright information

© Royal Dutch Association for the Advancement of Pharmacy 1993

Authors and Affiliations

  • W. J. M. Underberg
    • 1
  • J. H. Beijnen
    • 2
  1. 1.Department of Pharmaceutical Analysis, Faculty of PharmacyUtrecht UniversityCA UtrechtThe Netherlands
  2. 2.Slotervaart Hospital/Netherlands Cancer InstituteEC AmsterdamThe Netherlands

Personalised recommendations