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Combined use of liquid chromatography with mass spectrometry and nuclear magnetic resonance for the identification of degradation compounds in an erythromycin formulation

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Abstract

A commercial erythromycin formulation containing erythromycin A (EA) as the major compound showed the presence of an unknown degradation compound that was co-eluted with erythromycin E (EE) in the European Pharmacopoeia (Ph. Eur.) liquid chromatographic (LC) method. The amount of the degradation compound increased with respect to time. To separate this unknown (UNK1), investigation was performed with different LC methods coupled to ultraviolet detection (LC-UV). With the present Ph. Eur. method, the degradation compound could not be well separated. However, with the most selective LC-UV method (XTerra method), two more degradation products (UNK2 and UNK3) were found in the formulation which could not be observed using other methods because of their poor separation. By combining the results obtained with LC-UV, LC/MS and LC/NMR, the degradation products were identified as pseudoerythromycin A hemiketal (PsEAHK), erythromycin A enol ether carboxylic acid and erythromycin C enol ether carboxylic acid. PsEAHK is known to be a base-catalysed degradation product of EA, whereas the other two degradation products were newly identified.

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Acknowledgement

The NMR part of this work was supported by the National Scientific Research Fund of Hungary, OTKA K73804.

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Authors and Affiliations

  1. Laboratory for Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, O&N2, PB 923, Herestraat 49, 3000, Leuven, Belgium

    M. Pendela, E. Haghedooren, L. Van den Bossche, A. Van Schepdael, J. Hoogmartens & E. Adams

  2. Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre u. 9, 1092, Budapest, Hungary

    S. Béni & B. Noszál

Authors
  1. M. Pendela
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  2. S. Béni
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  3. E. Haghedooren
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  4. L. Van den Bossche
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  5. B. Noszál
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  6. A. Van Schepdael
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  8. E. Adams
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Correspondence to E. Adams.

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Pendela, M., Béni, S., Haghedooren, E. et al. Combined use of liquid chromatography with mass spectrometry and nuclear magnetic resonance for the identification of degradation compounds in an erythromycin formulation. Anal Bioanal Chem 402, 781–790 (2012). https://doi.org/10.1007/s00216-011-5450-0

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  • DOI: https://doi.org/10.1007/s00216-011-5450-0

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