All levothyroxines are equal, but some are more equal than others...
At last, a bit more evidence as to why the various levothyroxine products might vary in impact. With 24 novel compounds, it is impossible to know their impact on our bodies. There cannot have been investigation of them if no-one knew what they are!
Although we regularly see claims about the excipients being the cause of issues, I have long wondered about impurities. For example, perhaps, for some, it isn't the lactose itself, that is the issue (even if somewhat lactose intolerant) but some compound formed by reaction between levothyroxine and lactose?
Sadly, the full paper is behind a paywall and, even if we gained access, I doubt we would see manufacturers' names.
J Pharm Biomed Anal. 2016 Dec 14;135:140-152. doi: 10.1016/j.jpba.2016.12.002. [Epub ahead of print]
Levothyroxine sodium revisited: A wholistic structural elucidation approach of new impurities via HPLC-HRMS/MS, on-line H/D exchange, NMR spectroscopy and chemical synthesis.
Ruggenthaler M1, Grass J2, Schuh W2, Huber CG3, Reischl RJ4.
1SANDOZ 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.
2SANDOZ GmbH, Biochemiestraße 10, A-6250 Kundl/Tirol, Austria.
3Department of Molecular Biology, Division of Chemistry and Bioanalytics,University of Salzburg, Hellbrunner Straße 34, A-5020 Salzburg, Austria.
4Department of Molecular Biology, Division of Chemistry and Bioanalytics,University of Salzburg, Hellbrunner Straße 34, A-5020 Salzburg, Austria. Electronic address: email@example.com.
The structural elucidation of unknown pharmaceutical impurities plays an important role in the quality control of newly developed and well-established active pharmaceutical ingredients (APIs). The United States Pharmacopeia (USP) monograph for the API Levothyroxine Sodium, a synthetic thyroid hormone, features two high pressure liquid chromatography (HPLC) methods using UV-VIS absorption detection to determine organic impurities in the drug substance. The impurity profile of the first USP method ("Procedure 1") has already been extensively studied, however for the second method ("Procedure 2"), which exhibits a significantly different impurity profile, no wholistic structural elucidation of impurities has been performed yet. Applying minor modifications to the chromatographic parameters of USP "Procedure 2" and using various comprehensive structural elucidation methods such as high resolution tandem mass spectrometry with on-line hydrogen-deuterium (H/D) exchange or two-dimensional nuclear magnetic resonance spectroscopy (NMR) we gained new insights about the complex impurity profile of the synthetic thyroid hormone. This resulted in the characterization of 24 compounds previously unknown to literature and the introduction of two new classes of Levothyroxine Sodium impurities. Five novel compounds were unambiguously identified via isolation or synthesis of reference substances and subsequent NMR spectroscopic investigation. Additionally, Collision-Induced Dissociation (CID)-type fragmentation of identified major impurities as well as neutral loss fragmentation patterns of many characterized impurities were discussed.
Copyright © 2016 Elsevier B.V. All rights reserved.
HDX; LC-MS; Levothyroxine; On-line H/D Exchange; Pharmaceutical impurities; Thyroid hormone
[PubMed - as supplied by publisher]