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Comparison of Bevacizumab Quantification Results in Plasma of Non-small Cell Lung Cancer Patients Using Bioanalytical Techniques Between LC-MS/MS, ELISA, and Microfluidic-based Immunoassay

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Abstract

The development of analytical techniques to study therapeutic monoclonal antibodies is expected to be useful for pharmacokinetic analysis and for the development of therapeutic indexes to determine dosage standards. To date, the blood concentration of antibody drugs has been analyzed by the enzyme-linked immunosorbent assay (ELISA). However, with the development of mass spectrometry and microfluidization technologies, the assay implication is drastically changing. We have developed an analytical validation method for many monoclonal antibodies and Fc-fusion proteins using Fab-selective proteolysis nSMOL coupled with liquid chromatography-mass spectrometry (LC-MS/MS). However, the correlation between the analyzed data characterization and the referable value from individual measurement techniques has not been adequately discussed. Therefore, in this study, we discussed in detail the relationship of the bioanalytical data from three different techniques, LC-MS/MS, ELISA, and microfluidic immunoassay, using 245 clinical plasma samples from non-small cell lung cancer patients treated with bevacizumab. The quantified concentration data of bevacizumab in human plasma indicated that the results obtained were almost the same correlation regardless of which technique was used. And the referable value from LC-MS/MS and microfluidic immunoassay were similar and correlated compared with ELISA.

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Acknowledgements

This study of the LBA-based assay was performed by Dr. Naoe Yamane of CMIC Pharma Science (Tokyo, Japan).

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Authors and Affiliations

  1. Leading Technology of Bioanalysis and Protein Chemistry, Shimadzu Corporation, Kyoto, Japan

    Noriko Iwamoto, Megumi Takanashi & Takashi Shimada

  2. Shimadzu Bioscience Research Partnership, Shimadzu Scientific Instruments, 21720 23rd Dr SE #250, Bothell, Washington, 98021, USA

    Noriko Iwamoto & Takashi Shimada

  3. Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara, Japan

    Jiichiro Sasaki

  4. Division of Molecular Pharmacology, National Cancer Center Research Institute, Tokyo, Japan

    Akinobu Hamada

  5. Department of Pharmacology and Therapeutics, Fundamental Innovative Oncology Core, National Cancer Center Research Institute, Tokyo, Japan

    Akinobu Hamada

  6. Division of Clinical Pharmacology and Translational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Akinobu Hamada

Authors
  1. Noriko Iwamoto
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  2. Megumi Takanashi
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  3. Takashi Shimada
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  4. Jiichiro Sasaki
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  5. Akinobu Hamada
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Corresponding authors

Correspondence to Takashi Shimada or Akinobu Hamada.

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This study was reviewed and approved by the relevant institutional review boards and signed informed consent was obtained from all patients prior to participation. The procedures were in accordance with the Helsinki Declaration.

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Iwamoto, N., Takanashi, M., Shimada, T. et al. Comparison of Bevacizumab Quantification Results in Plasma of Non-small Cell Lung Cancer Patients Using Bioanalytical Techniques Between LC-MS/MS, ELISA, and Microfluidic-based Immunoassay. AAPS J 21, 101 (2019). https://doi.org/10.1208/s12248-019-0369-z

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  • DOI: https://doi.org/10.1208/s12248-019-0369-z

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