So, over sixty years after producing liothyronine, a company has actually analysed the impurities!
I guess the next steps would be to do the same type of analysis across all available products - first of liothyronine sodium as an ingredient, second of end-product tablets. (I rather assume that this analysis was of the substance produced by Sandoz themselves.) Then to identify which of the impurities might be of significance to those taking liothyronine. Of course, many of them could be of no consequence whatsoever, whether because of the amount or lack of biological activity.
If any of these impurities are significant, this might help to explain the remarkable range of opinions that patients have of the different makes.
J Pharm Biomed Anal. 2017 May 30;143:147-158. doi: 10.1016/j.jpba.2017.05.039. [Epub ahead of print]
Impurity profiling of liothyronine sodium by means of reversed phase HPLC, high resolution mass spectrometry, on-line H/D exchange and UV/Vis absorption.
Ruggenthaler M1, Grass J2, Schuh W2, Huber CG3, Reischl RJ4.
1 SANDOZ GmbH, Biochemiestraße 10, A-6250 Kundl/Tirol, Austria; Department of Molecular Biology, Division of Chemistry and Bioanalytics, University of Salzburg, Hellbrunner Straße 34, A-5020 Salzburg, Austria.
2 SANDOZ GmbH, Biochemiestraße 10, A-6250 Kundl/Tirol, Austria.
3 Department of Molecular Biology, Division of Chemistry and Bioanalytics, University of Salzburg, Hellbrunner Straße 34, A-5020 Salzburg, Austria.
4 Department of Molecular Biology, Division of Chemistry and Bioanalytics, University of Salzburg, Hellbrunner Straße 34, A-5020 Salzburg, Austria. Electronic address: firstname.lastname@example.org.
For the first time, a comprehensive investigation of the impurity profile of the synthetic thyroid API (active pharmaceutical ingredient) liothyronine sodium (LT3Na) was performed by using reversed phase HPLC and advanced structural elucidation techniques including high resolution tandem mass spectrometry (HRMS/MS) and on-line hydrogen-deuterium (H/D) exchange. Overall, 39 compounds were characterized and 25 of these related substances were previously unknown to literature. The impurity classification system recently developed for the closely related API levothyroxine sodium (LT4Na) could be applied to the newly characterized liothyronine sodium impurities resulting in a wholistic thyroid API impurity classification system. Furthermore, the mass-spectrometric CID-fragmentation of specific related substances was discussed and rationalized by detailed fragmentation pathways. Moreover, the UV/Vis absorption characteristics of the API and selected impurities were investigated to corroborate chemical structure assignments derived from MS data.
Copyright © 2017 Elsevier B.V. All rights reserved.
API analysis; H/D exchange; HDX; HRMS; HRMS/MS; Hormone deficiency; Hypothyroidism; Impurity profiling; LT3Na; Liothyronine; Liothyronine sodium; Thyroxine; UV Vis spectroscopy
The journal page is here - with paper behind paywall. There is a pretty picture but too small to be of much use!
The equivalent abstract (not full paper, I am afraid) about levothyroxine may be found here: