Skip to main content

Kinetics of Degradation of Levothyroxine in Aqueous Solution and in Solid State

Pharmaceutical Research volume 9, pages 131–137 (1992)Cite this article

Abstract

The kinetics of the deiodination of levothyroxine in aqueous solution were studied over the pH range 1 to 12. Temperature dependence of the reaction was also studied. The log k − pH profile indicated that the kinetics of deiodination include proton attack on the anion and dianion in acidic solution and water attack on the anion and dianion in alkaline solution. A possible mechanism of the deiodination was discussed. The solid-state stability of levothyroxine sodium was studied at elevated temperatures; and the compound was found to undergo deamination on heating. The decomposition follows biphasic first-order kinetics, with the most rapid decomposition occurring at the beginning of heating.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

REFERENCES

  1. E. R. Barnhart. Physicians' Desk Reference, Medical Economics, Oradell, NJ, 1989, pp. 1830–1831.

    Google Scholar 

  2. A. L. Reviczky and S. B. Nagy. Untersuchung der Thyroxindejodisation mit instrumenteller analytischer Methode. Endokrinologie 56:81–91 (1970).

    Google Scholar 

  3. J. B. Stanbury. Deiodination of the iodinated amino acids. Ann. N.Y. Acad. Sci. 86 (Part 2):417–439 (1960).

    Google Scholar 

  4. T. Jolin, G. Morreale de Escobar, and F. Escobar del Rey. Pitfalls in studies of in vitro deiodination of thyroxine. Endocrinology 78:7–15 (1966).

    Google Scholar 

  5. H. S. Harned and B. B. Owen. The Physical Chemistry of Electrolyte Solutions, Reinhold, New York, 1958, p. 716.

    Google Scholar 

  6. B. H. Lippold and J. F. Lichey. Löslichkeits-pH Profile mehrprotoniger Arzneistoffe am Beispiel des assoziierenden Dimetindens und des zwitterionischen Liothyronines. Arch. Pharm. (Weinheim) 314:541–556 (1981).

    Google Scholar 

  7. A. Post and R. J. Warren. Sodium levothyroxine. In K. Florey (ed.), Analytical Profiles of Drug Substances, Vol. 5, Academic Press, New York, 1976, pp. 226–281.

    Google Scholar 

  8. E. Grovenstein, Jr., and N. S. Aprahamian. Aromatic Halogenation. II. Kinetics and mechanism of iodination of 4-nitrophenol and 4-nitrophenol-2,6-d2. J. Am. Chem. Soc. 84:212–220 (1962).

    Google Scholar 

  9. J. Hine. Physical Organic Chemistry, McGraw-Hill, New York, 1962, p. 358.

    Google Scholar 

  10. J. F. Brower, D. Y. Toler, and J. C. Reepmeyer. Determination of sodium levothyroxine in bulk, tablet, and injection formulations by high-performance liquid chromatography. J. Pharm. Sci. 73:1315–1317 (1984).

    Google Scholar 

  11. A. A. Frost and R. G. Pearson. Kinetics and Mechanism, Wiley, New York, 1961, pp. 162–164.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Analytical and Physical Chemistry Department, Rhône-Poulenc Rorer Central Research, 500 Virginia Drive, Building No. 5, Fort Washington, Pennsylvania, 19034

    Chong Min Won

Authors
  1. Chong Min Won
    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

Won, C.M. Kinetics of Degradation of Levothyroxine in Aqueous Solution and in Solid State. Pharm Res 9, 131–137 (1992). https://doi.org/10.1023/A:1018952415732

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018952415732

  • levothyroxine
  • liothyronine
  • degradation, deiodination
  • pH effect
  • solid-state stability