Verification between original and biosimilar therapeutic antibody infliximab using nSMOL coupled LC-MS bioanalysis in human serum

Noriko Iwamoto, Kotoko Yokoyama, Megumi Takanashi, Atsushi Yonezawa, Kazuo Matsubara, Takashi Shimada

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


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 Remicade™ and its biosimilar product using our nano-surface and molecular-orientation limited proteolysis (nSMOL) technology coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The nSMOL chemistry has a unique property of Fab-selective 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.

Original languageEnglish
Pages (from-to)495-505
Number of pages11
JournalCurrent Pharmaceutical Biotechnology
Issue number6
Publication statusPublished - 2018
Externally publishedYes


  • Bioanalysis
  • Biosimilar
  • Clinical pharmacokinetics
  • Infliximab
  • LC-MS
  • Therapeutic drug monitoring
  • nSMOL

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science


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