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Isolation and identification of three new isomer impurities in milbemycin oxime drug substance

The Journal of Antibiotics volume 78, pages 106–112 (2025)Cite this article

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Abstract

In an effort to identification of the unknown impurities in milbemycin oxime (MO) bulk drug, three impurities 1, 2 and 3 were isolated by two-dimensional (2 D) preparation method (Agilent Zorbax-C3 preparative column and Sepax Amethyst C18-H preparative column). Based on the extensive NMR analysis and ESIMS data, the structures of the three impurities were established as 14-desmethyl-14-ethyl-MO A4 (1), 24-desmethyl-24-ethyl-MO A4 (2) and 12-desmethyl-12-ethyl-MO A4 (3), respectively. They are the new isomer impurities of MO D and most likely originate from the oxidation and oximation of natural milbemycin homologs present in the original fermentation broth.

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Acknowledgements

This research was financially supported by Zhejiang Provincial Natural Science Foundation of China (Grant No. LGN22B020002), School-enterprise Cooperation Project from Domestic Visiting Engineers of Colleges and Universities (Grant No.: FG2023314), Huzhou Public Welfare Research Project (2021GZ25) and Taizhou Science and Technology Plan Project (24nyb10).

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Authors and Affiliations

  1. Zhejiang Key Laboratory of Biology and Ecological Regulation of Crop Pathogens and Insect, College of Life Science, Huzhou University, Huzhou, China

    Xiaohan Ren, Shaoyong Zhang, Huan Qi & Jidong Wang

  2. Zhejiang Qianjiang Biochemical Co., Ltd, Haining, China

    Jianwei Lu & Yefei Wu

  3. Key Laboratory of Horticultural Biotechnology of Taizhou, School of Agriculture and Bioengineering, Taizhou Vocational College of Science and Technology, Taizhou, China

    Hui Zhang

  4. Zhejiang Huida Biotech Co., Ltd, Hangzhou, China

    Linghui Zheng

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  1. Xiaohan Ren
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  2. Jianwei Lu
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Correspondence to Jidong Wang or Linghui Zheng.

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Ren, X., Lu, J., Wu, Y. et al. Isolation and identification of three new isomer impurities in milbemycin oxime drug substance. J Antibiot 78, 106–112 (2025). https://doi.org/10.1038/s41429-024-00791-7

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