Repository: Freie Universit├Ąt Berlin, Math Department

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

Neu, V. and Bielow, C. and Schneider, P. and Reinert, K. and Stuppner, H. and Huber, C. (2013) 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. Analytical Chemistry, 85 (4). pp. 2385-2390. ISSN 0003-2700

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Official URL: http://pubs.acs.org/doi/abs/10.1021/ac303404e

Abstract

A reaction scheme was derived for the thermal degradation of thyroxine in the solid state, using data obtained from ultrahigh-performance liquid chromatography and high-resolution mass spectrometry (UHPLC-HRMS). To study the reaction mechanism and kinetics of the thermal degradation of the pharmaceutical in the solid state, a workflow was developed by generating compound-specific, time-dependent degradation or formation curves of at least 13 different degradation products. Such curves allowed one to distinguish between first- and second-generation degradation products, as well as impurities resulting from chemical synthesis. The structures of the degradation products were derived from accurate molecular masses and multistage mass spectrometry. Deiodination and oxidative side chain degradation were found to be the major degradation reactions, resulting in the formation of deiodinated thyroxines, as well as acetic acid, benzoic acid, formaldehyde, acetamide, hydroxyacetic acid, oxoacetic acid, hydroxyacetamide, or oxoacetamide derivatives of thyroxine or deiodinated thyroxine. Upon additional structural verification of mass spectrometric data using nuclear magnetic resonance spectroscopy, this comprehensive body of data sheds light on an elaborate, radical-driven reaction scheme, explaining the presence or formation of impurities in thermally stressed thyroxine.

Item Type:Article
Subjects:Mathematical and Computer Sciences > Computer Science
Divisions:Department of Mathematics and Computer Science > Institute of Computer Science > Algorithmic Bioinformatics Group
ID Code:1398
Deposited By: Anja Kasseckert
Deposited On:18 Mar 2014 15:10
Last Modified:18 Mar 2014 15:10

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