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Current Pharmaceutical Biotechnology


ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Research Article

Verification between Original and Biosimilar Therapeutic Antibody Infliximab Using nSMOL Coupled LC-MS Bioanalysis in Human Serum

Author(s): Noriko Iwamoto, Kotoko Yokoyama, Megumi Takanashi, Atsushi Yonezawa, Kazuo Matsubara and Takashi Shimada*

Volume 19, Issue 6, 2018

Page: [495 - 505] Pages: 11

DOI: 10.2174/1389201019666180703093517

open access plus


Background: Infliximab (IFX) is a chimeric therapeutic monoclonal antibody targeting tumor necrosis factor alpha (TNFα)-mediated inflammatory immune diseases. However, despite of an initial good clinical response, decrease in response to long-term treatment is a common observation.

Objective: Recent studies suggest that IFX level in circulation has a correlation with clinical bioavailability. Therefore, the management of IFX dosage for individual manifestation by IFX monitoring may be valuable for the improvement of therapeutic response and outcomes.

Method: In order to develop a broad IFX therapeutic monitoring in human serum, we have developed the validated IFX bioanalysis for RemicadeTM and its biosimilar product using our nano-surface and molecular-orientation limited proteolysis (nSMOL) technology coupled with liquid chromatographytandem mass spectrometry (LC-MS/MS). The nSMOL chemistry has a unique property of Fabselective proteolysis, and makes it possible a global bioanalysis for many monoclonal antibodies.

Results: The quantitation range of IFX in serum was from 0.293 to 300 μg/ml with good linearity. Quantitation verification at the concentrations of 0.293, 0.879, 14.1 and 240 µg/ml was within 1.56- 7.53% of precision and 98.9-111% of accuracy using H-chain signature peptide SINSATHYAESVK. Moreover, cross-verified bioanalysis of Remicade quantitation using biosimilar standard, and its opposite combination, obtained an identical and inter-comparative results.

Conclusion: The nSMOL strategy has the potential as a practical therapeutic monitoring technology in IFX therapeutic applications.

Keywords: Infliximab, biosimilar, nSMOL, LC-MS, bioanalysis, clinical pharmacokinetics, therapeutic drug monitoring.

Graphical Abstract

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