Thyroid UK
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Impurity profiling of liothyronine sodium by reversed phase HPLC, high res mass spectrometry, on-line H/D exchange + UV/Vis absorption

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.

Author information

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:


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

PMID: 28599168

DOI: 10.1016/j.jpba.2017.05.039

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:

14 Replies

That sounds interest but without my scientific head on which is tarninshing fast I can't make up my mind whether it is suggesting we have never had the biologically correct formula or 'recent' changes have not kept the correct formulation. But either way it could explain a lot! Will save for later!

Thanks for posting

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What it is saying is that we don't get pure liothyronine but a mixture of liothyronine with a load of other substances in it. Until now, they have not put in the effort to identify these other substances properly. This paper does that.

It is inevitable that there will be other substances present but until we know what they are, and in what quantities, we really cannot be sure of their impact on us.


Thanks what I was thinking and that advances in testing have shown these things to be present. My very limited experience in that was matching something with a known printout but finding other evidence must be a bit like looking for a needle in a haystack. Its never going to be as obvious as one would like it to be but I hope it's not going to be one an excuse to take it off the market or could it give credence to NDT! Science can be wonderful or a nightmare. Let's hope it's not a nightmare!

I woundnt be surprised if different brands have something added that other manufactures haven't used to purposely make it different so no charge of copying could be levied but I would like to think that any 'extra' put in the mix isn't harmful but has at least acceptable and even necessary additives in their opinion. It will be interesting to see where it leads


This analysis was of the liothyronine powder - before being made up into tablets. So I think what they found were genuine impurities that were not intended to be there at all.

We have no idea if this liothyronine powder is used in one or many actual tablets!

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Well ploughed through at least the headings for papers they have touched on and as we have also said we have a long list of potential problems which thankfully we don't get all of them but can get any of them! So ms y considerations shouldn't be unexpected. It would be interesting though to have comparisons to get some sort of perspective. The number of things they have found seem a lot but we have no idea of what other medicines could throw up and, as you say, be interesting to compare with other brands of T3 and also T4 preparations. Science can and will move forward thanks to a dedicated section of society who always strive to improve on things. It just can take a lot of time to reach perfection.

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It might not only be liothyronine that is impure but also levothyroxine, have they looked into that?


Read the last sentence and link on the original post. :-)


As you say, it's behind a high paywall. Do you think NDT has as many impurities?


Desiccated thyroid will have lots and lots of other substances in it!

Just think, a grain (say 60 milligrams) of desiccated thyroid has only 38 micrograms of T4 and 9 micrograms of T3. So there are over 59 milligrams of other substances!

We can expect that the impurities in desiccated thyroid will mostly be substances that occur in animal thyroids - we still know next to nothing about what the impurities in synthetic thyroid hormones are, nor do we know their possible impact.


Yuk, I don't like the thought of the impurities. I've been trying to work out what might interfere with the B12 cycle or synthesis...


Funny, though, how often we see things like sea salt and Himalayan salt praised to the rooftops - very largely because of the impurities they contain! :-)


I think it's the idea that the impurities aren't meant to be there that's worrying. We assume that sea salt has developed in balance with nature but it's something we can avoid if we want. We can't avoid our tablets!!


On the other hand, things like almonds and fruit stone kernels often contain considerable amounts of cyanide - and that is surely in balance with nature! But something we really don't want as an impurity.



It's why we don't eat them!!!