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J Pharm Biomed Anal. 2017 Sep 5;143:147-158. doi: 10.1016/j.jpba.2017.05.039. Epub 2017 May 30.

Impurity profiling of liothyronine sodium by means of reversed phase HPLC, high resolution mass spectrometry, on-line H/D exchange and UV/Vis absorption.

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: roland.reischl@sbg.ac.at.

Abstract

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.

KEYWORDS:

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
[Indexed for MEDLINE]

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