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Separation and Characterization of New Components and Impurities in Leucomycin by Multiple Heart-Cutting Two-Dimensional Liquid Chromatography Combined with Ion Trap/Time-of-Flight Mass Spectrometry

  • Jian Wang
  • Guijun Liu
  • Yu Xu
  • Bingqi Zhu
  • Zhijian WangEmail author
Original
  • 9 Downloads

Abstract

In this study, nine new components and six impurities in leucomycin were discovered. A method was developed for the separation and characterization of new components and impurities in leucomycin by multiple heart-cutting two-dimensional liquid chromatography combined with ion trap/time-of-flight mass spectrometry in both positive and negative electrospray ionization modes. With this method, a non-volatile buffer solution was used as mobile phase in the first-dimensional system for good separation. Eluent of each peak from the first-dimensional system was trapped by a switching valve and sent to the liquid chromatography-mass spectrometry system using a volatile mobile phase. The complete fragmentation patterns of the new components and degradation impurities were deduced based on MSn data. The structures of nine new components in leucomycin were deduced as unsaturated ketone in the 16-membered ring of leucomycin. The structures of six impurities were characterized for the first time, four of which were acid degradation products, and the other two were process impurities. The correlation between impurities and the purification process of leucomycin was also studied. The degradation impurities were produced during purification of leucomycin fermentation broth, which requires a low-pH environment. Based on the characterization of impurities, this study not only revealed the mechanism of impurity production, thus providing guidance to pharmaceutical companies for manufacturing process improvement and impurity reduction, but also provided a scientific basis for further improvement of official monographs in pharmacopoeias.

Keywords

Kitasamycin Leucomycin Impurity Multiple heart-cutting two-dimensional liquid chromatography Ion trap/time-of-flight mass spectrometry 

Notes

Acknowledgements

This work was supported by Key Technologies and Standards for Drug Consistency Assessment of National Science and Technology Major Project (No. 2017ZX09101001).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

10337_2019_3754_MOESM1_ESM.doc (2.7 mb)
Supplementary material 1 (DOC 2724 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Zhejiang University of TechnologyHangzhouChina
  2. 2.Zhejiang Institute for Food and Drug ControlHangzhouChina

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