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Detection of low-abundance impurities in synthetic thyroid hormones by stationary phase optimized liquid chromatography–mass spectrometry

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Abstract

The transfer of a gradient method to an isocratic or multistep gradient method employing stationary phase optimized liquid chromatography facilitated a reduction in analysis time by 50% and significantly improved the mass spectrometric detectability of impurities in synthetic thyroid hormones. Four column segments packed with different stationary phases were combined into a single chromatographic column, which allowed the separation and photometric as well as mass spectrometric detection of thyroid compounds in less than 30 min under isocratic- or step gradient elution conditions with 0.10% acetic acid/acetonitrile. Signal instability and baseline drift during detection by negative electrospray ionization time-of-flight mass spectrometry were minimized by optimizing the spray parameters for each individual elution step. This resulted in improved detectabilities and higher mass spectral quality, especially for low-abundance components in the sample mixture. The method was applied to the separation and detection of the low-abundance impurities formed upon the thermal stressing of a sample of synthetic levothyroxine.

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Acknowledgements

Financial support by Bischoff Analysentechnik und -geräte GmbH (Leonberg, Germany) and helpful discussions with K. Bischoff and S. Lamotte are gratefully acknowledged.

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Authors and Affiliations

  1. Instrumental Analysis and Bioanalysis, Department of Chemistry, Saarland University, P.O. Box 151150, 66041, Saarbrücken, Germany

    Iris Gostomski

  2. Peptido GmbH, Am Kraftwerk 6, 66450, Bexbach, Germany

    Ralf Braun

  3. Department of Molecular Biology, Paris-Lodron-University, Hellbrunner Strasse 34, 5020 Salzburg, Austria

    Christian G. Huber

Authors
  1. Iris Gostomski
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  2. Ralf Braun
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  3. Christian G. Huber
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Correspondence to Christian G. Huber.

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Gostomski, I., Braun, R. & Huber, C.G. Detection of low-abundance impurities in synthetic thyroid hormones by stationary phase optimized liquid chromatography–mass spectrometry. Anal Bioanal Chem 391, 279–288 (2008). https://doi.org/10.1007/s00216-008-1920-4

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  • DOI: https://doi.org/10.1007/s00216-008-1920-4

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