Skip to main content

Advertisement

SpringerLink
Log in

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

  • Research Article
  • Published:
The AAPS Journal Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Chen SC, Quartino A, Polhamus D, Riggs M, French J, Wang X, et al. Population pharmacokinetics and exposure-response of trastuzumab emtansine in advanced breast cancer previously treated with >/=2 HER2-targeted regimens. Br J Clin Pharmacol. 2017;83(12):2767–77. https://doi.org/10.1111/bcp.13381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Geukes Foppen MH, Rozeman EA, van Wilpe S, Postma C, Snaebjornsson P, van Thienen JV, et al. Immune checkpoint inhibition-related colitis: symptoms, endoscopic features, histology and response to management. ESMO Open. 2018;3(1):e000278. https://doi.org/10.1136/esmoopen-2017-000278.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Nishidate M, Hayashi M, Aikawa H, Tanaka K, Nakada N, Miura SI, et al. Applications of MALDI mass spectrometry imaging for pharmacokinetic studies during drug development. Drug Metab Pharmacokinet. 2019;34:209–16. https://doi.org/10.1016/j.dmpk.2019.04.006.

    Article  CAS  PubMed  Google Scholar 

  4. Liu X, Lukowski JK, Flinders C, Kim S, Georgiadis RA, Mumenthaler SM, et al. MALDI-MSI of immunotherapy: mapping the EGFR-targeting antibody Cetuximab in 3D colon-cancer cell cultures. Anal Chem. 2018;90(24):14156–64. https://doi.org/10.1021/acs.analchem.8b02151.

    Article  CAS  PubMed  Google Scholar 

  5. Randall EC, Emdal KB, Laramy JK, Kim M, Roos A, Calligaris D, et al. Integrated mapping of pharmacokinetics and pharmacodynamics in a patient-derived xenograft model of glioblastoma. Nat Commun. 2018;9(1):4904. https://doi.org/10.1038/s41467-018-07334-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Roussey JA, Viglianti SP, Teitz-Tennenbaum S, Olszewski MA, Osterholzer JJ. Anti-PD-1 antibody treatment promotes clearance of persistent Cryptococcal lung infection in mice. J Immunol. 2017;199(10):3535–46. https://doi.org/10.4049/jimmunol.1700840.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lee CH, Romain G, Yan W, Watanabe M, Charab W, Todorova B, et al. IgG Fc domains that bind C1q but not effector Fcgamma receptors delineate the importance of complement-mediated effector functions. Nat Immunol. 2017;18(8):889–98. https://doi.org/10.1038/ni.3770.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Atzori F, Tabernero J, Cervantes A, Prudkin L, Andreu J, Rodriguez-Braun E, et al. A phase I pharmacokinetic and pharmacodynamic study of dalotuzumab (MK-0646), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res. 2011;17(19):6304–12. https://doi.org/10.1158/1078-0432.CCR-10-3336.

    Article  CAS  PubMed  Google Scholar 

  9. Saito M, Kawakami Y, Yamashita K, Nasuno H, Ishimine YU, Fukuda K, et al. HER2-positive gastric cancer identified by serum HER2: a case report. Oncol Lett. 2016;11(6):3575–8. https://doi.org/10.3892/ol.2016.4470.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tabernero J, Ohtsu A, Muro K, Van Cutsem E, Oh SC, Bodoky G, et al. Exposure-response analyses of Ramucirumab from two randomized, phase III trials of second-line treatment for advanced gastric or gastroesophageal junction cancer. Mol Cancer Ther. 2017;16(10):2215–22. https://doi.org/10.1158/1535-7163.MCT-16-0895.

    Article  CAS  PubMed  Google Scholar 

  11. Shah N, Mohammad AS, Saralkar P, Sprowls SA, Vickers SD, John D, et al. Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases. Pharmacol Res. 2018;132:47–68. https://doi.org/10.1016/j.phrs.2018.03.021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Li M, Kroetz DL. Bevacizumab-induced hypertension: clinical presentation and molecular understanding. Pharmacol Ther. 2018;182:152–60. https://doi.org/10.1016/j.pharmthera.2017.08.012.

    Article  CAS  PubMed  Google Scholar 

  13. Baker JHE, Kyle AH, Reinsberg SA, Moosvi F, Patrick HM, Cran J, et al. Heterogeneous distribution of trastuzumab in HER2-positive xenografts and metastases: role of the tumor microenvironment. Clin Exp Metastasis. 2018;35(7):691–705. https://doi.org/10.1007/s10585-018-9929-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhao X, Suryawanshi S, Hruska M, Feng Y, Wang X, Shen J, et al. Assessment of nivolumab benefit-risk profile of a 240-mg flat dose relative to a 3-mg/kg dosing regimen in patients with advanced tumors. Ann Oncol. 2017;28(8):2002–8. https://doi.org/10.1093/annonc/mdx235.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Iwamoto N, Shimada T, Umino Y, Aoki C, Aoki Y, Sato TA, et al. Selective detection of complementarity-determining regions of monoclonal antibody by limiting protease access to the substrate: nano-surface and molecular-orientation limited proteolysis. Analyst. 2014;139(3):576–80. https://doi.org/10.1039/c3an02104a.

    Article  CAS  PubMed  Google Scholar 

  16. Cruz E, Kayser V. Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy. Biologics. 2019;13:33–51. https://doi.org/10.2147/BTT.S166310.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Yang Z, Hayes M, Fang X, Daley MP, Ettenberg S, Tse FL. LC-MS/MS approach for quantification of therapeutic proteins in plasma using a protein internal standard and 2D-solid-phase extraction cleanup. Anal Chem. 2007;79(24):9294–301. https://doi.org/10.1021/ac0712502.

    Article  CAS  PubMed  Google Scholar 

  18. Gong C, Zheng N, Zeng J, Aubry AF, Arnold ME. Post-pellet-digestion precipitation and solid phase extraction: a practical and efficient workflow to extract surrogate peptides for ultra-high performance liquid chromatography--tandem mass spectrometry bioanalysis of a therapeutic antibody in the low ng/mL range. J Chromatogr A. 2015;1424:27–36. https://doi.org/10.1016/j.chroma.2015.10.049.

    Article  CAS  PubMed  Google Scholar 

  19. Iwamoto N, Shimada T, Terakado H, Hamada A. Validated LC-MS/MS analysis of immune checkpoint inhibitor Nivolumab in human plasma using a Fab peptide-selective quantitation method: nano-surface and molecular-orientation limited (nSMOL) proteolysis. J Chromatogr B Anal Technol Biomed Life Sci. 2016;1023-1024:9–16. https://doi.org/10.1016/j.jchromb.2016.04.038.

    Article  CAS  Google Scholar 

  20. Iwamoto N, Umino Y, Aoki C, Yamane N, Hamada A, Shimada T. Fully validated LCMS bioanalysis of Bevacizumab in human plasma using nano-surface and molecular-orientation limited (nSMOL) proteolysis. Drug Metab Pharmacokinet. 2016;31(1):46–50. https://doi.org/10.1016/j.dmpk.2015.11.004.

    Article  CAS  PubMed  Google Scholar 

  21. Iwamoto N, Shimada T. Recent advances in mass spectrometry-based approaches for proteomics and biologics: great contribution for developing therapeutic antibodies. Pharmacol Ther. 2018;185:147–54. https://doi.org/10.1016/j.pharmthera.2017.12.007.

    Article  CAS  PubMed  Google Scholar 

  22. Honda N, Lindberg U, Andersson P, Hoffmann S, Takei H. Simultaneous multiple immunoassays in a compact disc-shaped microfluidic device based on centrifugal force. Clin Chem. 2005;51(10):1955–61. https://doi.org/10.1373/clinchem.2005.053348.

    Article  CAS  PubMed  Google Scholar 

  23. Myzithras M, Bigwarfe T, Waltz E, Li H, Ahlberg J, Rybina I, et al. Optimizing NBE PK/PD assays using the Gyrolab Affinity Software; conveniently within the bioanalyst's existing workflow. Bioanalysis. 2018;10(6):397–406. https://doi.org/10.4155/bio-2017-0251.

    Article  CAS  PubMed  Google Scholar 

  24. Pohl G, Shih Ie M. Principle and applications of digital PCR. Expert Rev Mol Diagn. 2004;4(1):41–7.

    Article  CAS  PubMed  Google Scholar 

  25. Nishio K, Gokon N, Hasegawa M, Ogura Y, Ikeda M, Narimatsu H, et al. Identification of a chemical substructure that is immobilized to ferrite nanoparticles (FP). Colloids Surf B: Biointerfaces. 2007;54(2):249–53. https://doi.org/10.1016/j.colsurfb.2006.10.039.

    Article  CAS  PubMed  Google Scholar 

  26. Iwamoto N, Hamada A, Shimada T. Antibody drug quantitation in coexistence with anti-drug antibodies on nSMOL bioanalysis. Anal Biochem. 2018;540-541:30–7. https://doi.org/10.1016/j.ab.2017.11.002.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

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

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Megumi Takanashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takashi Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiichiro Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akinobu Hamada
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Takashi Shimada or Akinobu Hamada.

Ethics declarations

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.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

ESM 1

(DOCX 33 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

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

KEY WORDS

Search

Navigation