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Quantitative Study of Impurities in Enzalutamide and Identification, Isolation, Characterization of Its Four Degradation Products Using HPLC, Semi-preparative LC, LC/ESI–MS and NMR Analyses

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Abstract

Enzalutamide was recently approved for the treatment of castration-resistant prostate cancer. In this study, the related substances in enzalutamide bulk substance were analyzed qualitatively and quantitatively. Four degradation products (Oxi, A9, P1 and P2) of enzalutamide were isolated using semi-preparative liquid chromatography and characterized using nuclear magnetic resonance and mass spectrometry. In addition, two reversed-phase liquid chromatography methods were developed for quantification of 13 potential impurities and the main constituent, respectively. These two methods were validated and applied during the impurity studies and quality control analysis of the laboratory-prepared samples of enzalutamide.

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Acknowledgements

The work was supported by the 2016 Shanghai Pujiang Talent Plan (No. 16PJ1432800).

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Authors and Affiliations

  1. Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, Shanghai, 201203, China

    Ainan Zhou, Lejun Ruan & Jianqi Li

  2. School of Pharmacy, Fudan University, Shanghai, 201203, China

    Ainan Zhou & Gengli Duan

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  1. Ainan Zhou
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  2. Lejun Ruan
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  3. Gengli Duan
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Correspondence to Jianqi Li.

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Zhou, A., Ruan, L., Duan, G. et al. Quantitative Study of Impurities in Enzalutamide and Identification, Isolation, Characterization of Its Four Degradation Products Using HPLC, Semi-preparative LC, LC/ESI–MS and NMR Analyses. Chromatographia 81, 1519–1531 (2018). https://doi.org/10.1007/s10337-018-3611-4

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  • DOI: https://doi.org/10.1007/s10337-018-3611-4

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