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Development of a Novel and Stability Indicating RP-HPLC-UV Method for Simultaneous Analysis of Carbetocin and Ten Impurities in Carbetocin Injection Products

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Abstract

A novel, simple and stability indicating reverse-phase high performance liquid chromatographic method with UV detection at 220 nm (RP-HPLC-UV) was established to realize the simultaneous analysis of carbetocin and ten related impurities. This paper performed the most comprehensive impurity profiling of carbetocin, including the synthesis-related impurities, the isomers of carbetocin and the degradants formed from the forced degradation research, the structures of which were tentatively identified by a two-dimensional liquid chromatography-mass spectrometry technology. The novelty of this RP-HPLC-UV method was demonstrated by its satisfactory resolution and selectivity, which was achieved using an YMC-pack C18 column kept at 40 ℃, and optimal organic modifier gradient. The mobile phase A was potassium dihydrogen phosphate buffer (pH 6.5)—acetonitrile (80:20, v/v), and the mobile phase B was potassium dihydrogen phosphate buffer (pH 6.5)—acetonitrile (72:28, v/v). The forced degradation research proved the stability-indicating capacity of the method and validation study was performed according to ICH requirements. In summary, this RP-HPLC-UV method could support the simultaneous determination of related substances of carbetocin in bulk drug and in pharmaceutical formulations.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This paper was supported by National Natural Science Foundation of China (No. 31872755, 81872811), Jiangsu Outstanding Youth Funding (BK20190007) and the Central Fundamental Research Funds for the Central Universities (02141438473).

Funding

National Natural Science Foundation of China (No. 31872755, 81872811); Jiangsu Outstanding Youth Funding (BK20190007); Central Fundamental Research Funds for the Central Universities (02141438473).

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Author notes

  1. Lining Yin and Yuye Huang have contributed equally.

Authors and Affiliations

  1. State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University and School of Life Sciences, Nanjing University, Nanjing, 210093, People’s Republic of China

    Lining Yin, Yuye Huang, Chao Wang, Hong Dong, Yibing Ding & Jinhui Wu

  2. Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing, 210023, People’s Republic of China

    Jinhui Wu

  3. The Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210093, People’s Republic of China

    Bin Huang

  4. Nanjing University, No. 22 Hankou Road, Gulou District, Nanjing, 210093, People’s Republic of China

    Bin Huang & Jinhui Wu

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  1. Lining Yin
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  2. Yuye Huang
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  3. Chao Wang
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  6. Bin Huang
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Correspondence to Bin Huang or Jinhui Wu.

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Yin, L., Huang, Y., Wang, C. et al. Development of a Novel and Stability Indicating RP-HPLC-UV Method for Simultaneous Analysis of Carbetocin and Ten Impurities in Carbetocin Injection Products. Chromatographia 84, 967–978 (2021). https://doi.org/10.1007/s10337-021-04083-2

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  • DOI: https://doi.org/10.1007/s10337-021-04083-2

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