Investigation of Reaction Mechanisms of Drug Degradation in the Solid State: A Kinetic Study Implementing Ultrahigh-Performance Liquid Chromatography and High-Resolution Mass Spectrometry for Thermally Stressed Thyroxine
Volker Neu, Chris Bielow, Peter Schneider, Knut Reinert, Hermann Stuppner, and Christian G. Huber

Abstract:
The mechanism and kinetics of the thermal degradation of the pharmaceutical thyroxine could be obtained by hyphenating ultrahigh-performance liquid chromatography with high-resolution mass spectrometry (UHPLC-HRMS). The analysis revealed the formation of at least 138 different degradation products. Thirteen of these were included in an elaborate reaction scheme describing the mechanism of their formation. Deiodination and oxidative side chain degradation were found to be the major degradation reactions. Complementation of the MS data using nuclear magnetic resonance spectroscopy allowed to further rationalize the formation of impurities in thermally stressed thyroxine.

A copy of the article can be accessed via  http://www.doi.org/ using the digital object identifier DOI: 10.1021/ac303404e (requires access to the Journal Analytical Chemistry) or upon reprint request from the corresponding author ()

Reviewed by Johann Brandstetter