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Development of a liquid chromatography-based versatile bioanalysis for bevacizumab based on pretreatment combining aptamer affinity purification and centrifugal ultrafiltration concentration

  • Special Issue: Original Paper
  • Frontiers of Separation Analysis
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Abstract

We report on the development of a versatile and accurate bioanalytical method for bevacizumab using a pretreatment method combining affinity purification with anti-idiotypic DNA aptamers and centrifugal ultrafiltration concentration, followed by liquid chromatography (LC)-fluorescence analysis. An affinity purification method using Sepharose beads as an affinity support removed immunoglobulin G and a large amount of coexisting substances in the serum sample. Purified bevacizumab was separated as a single peak by conventional LC and detected fluorometrically, showing good linearity (R2 = 0.999) in the range of 5–200 μg/mL, sufficient to analyze bevacizumab concentrations in the blood of bevacizumab-treated patients. By combining this purification method with a concentration method using a centrifugal filtration device that inhibits non-specific adsorption of bevacizumab, the quantitative range was reduced by a factor of 10 while showing good linearity (R2 = 0.999) in the 0.5–20 μg/mL range. The developed analytical method is expected to be used not only for general bioanalysis of therapeutic mAbs in clinical settings, but also for next-generation antibody drugs that show drug efficacy at low concentrations and for analysis of trace samples.

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Acknowledgements

This work was supported by JSPS KAKENHI, Grant Nos. 16K08200, 19H03360, 22K06550, and the TaNeDS project funded by Daiichi-Sankyo Co. Ltd.

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Authors and Affiliations

  1. Department of Analytical and Bioanalytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-Ku, Shizuoka, 422-8526, Japan

    Kenichiro Todoroki, Daichi Hamada, Tomohiro Yamada & Eiji Sugiyama

  2. Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Naka-Cho, Koganei, Japan

    Taro Saito, Yutaka Shimizu, Kaori Tsukakoshi & Kazunori Ikebukuro

  3. Laboratory of Analytical Chemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku, Nagoya, 468-8503, Japan

    Hajime Mizuno

  4. Laboratory of Community Pharmaceutical Practice and Science, Gifu Pharmaceutical University, Daigaku-Nishi 1-25-4, Gifu, 501-1196, Japan

    Hideki Hayashi

Authors
  1. Kenichiro Todoroki
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  2. Daichi Hamada
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  3. Tomohiro Yamada
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  5. Yutaka Shimizu
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  6. Eiji Sugiyama
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  7. Hajime Mizuno
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  9. Kaori Tsukakoshi
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  10. Kazunori Ikebukuro
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Corresponding author

Correspondence to Kenichiro Todoroki.

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Todoroki, K., Hamada, D., Yamada, T. et al. Development of a liquid chromatography-based versatile bioanalysis for bevacizumab based on pretreatment combining aptamer affinity purification and centrifugal ultrafiltration concentration. ANAL. SCI. 39, 1805–1811 (2023). https://doi.org/10.1007/s44211-023-00417-2

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  • DOI: https://doi.org/10.1007/s44211-023-00417-2

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