This paper is a fascinating study which performed detailed chemical analysis on levothyroxine products in order to identify degradation products and unexpected substances. This was partly the result of the reformulation of Merck levothyroxine from lactose to mannitol - and the consequences in several countries - especially France which was the first to receive the new formulation.
The paper is extremely heavy going in parts with highly technical language. Nonetheless, it is actually quite easy to skip most of that and read the explanatory parts which are much easier. We don't need to know how to perform the analyses! Only what they found.
Next time a doctor, a nurse, a pharmacist or anyone else tells you all levothyroxine products are the same, offer a copy of this study...
Advancing drug safety and mitigating health concerns: High-resolution mass spectrometry in the levothyroxine case study
Abstract
Levothyroxine is a drug with a narrow therapeutic index. Changing the drug formulation composition or switching between pharmaceutical brands can alter the bioavailability, which can result in major health problems. However, the increased adverse drug reactions have not been fully explained scientifically yet and a thorough investigation of the formulations is needed. In this study, we used a non-targeted analytical approach to examine the various levothyroxine formulations in detail and to reveal possible chemical changes. Ultra-high-performance liquid chromatography coupled with a data-independent acquisition high-resolution mass spectrometry (UHPLC-DIA-HRMS) was employed. UHPLC-DIA-HRMS allowed not only the detection of levothyroxine degradation products, but also the presence of non-expected components in the formulations. Among these, we identified compounds resulting from reactions between mannitol and other excipients, such as citric acid, stearate, and palmitate, or from reactions between an excipient and an active pharmaceutical ingredient, such as levothyroxine-lactose adduct. In addition to these compounds, undeclared phospholipids were also found in three formulations. This non-targeted approach is not common in pharmaceutical quality control analysis. Revealing the presence of unexpected compounds in drug formulations proved that the current control mechanisms do not have to cover the full complexity of pharmaceutical formulations necessarily.
And the first sentence of the conclusion:
This work was designed as an independent study with the aim to comprehensively investigate levothyroxine formulations and thus contribute to their quality and safety in response to previous significant health crises.
Full paper including PDF version are open access at link below.
https://www.sciencedirect.com/science/article/pii/S2095177924000674
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