Analysis of Glycoforms and Amino Acids in Infliximab and a Biosimilar Product Using New Method with LC/TOF-MS

Biosimilar products of therapeutic antibodies have been launched all over the world. They can relieve some of the economic burden of medicines. Although clinical trials have demonstrated the equivalency of biosimilar products with their reference product, biosimilar products are not commonly used in...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2018/11/01, Vol.41(11), pp.1716-1721
Main Authors: Tsuda, Masahiro, Otani, Yuki, Yonezawa, Atsushi, Masui, Sho, Ikemi, Yasuaki, Denda, Masaya, Sato, Yuki, Nakagawa, Shunsaku, Omura, Tomohiro, Imai, Satoshi, Nakagawa, Takayuki, Hayakari, Makoto, Matsubara, Kazuo
Format: Article
Language:English
Subjects:
Amino acids
Amino Acids - analysis
Antibodies, Monoclonal - analysis
biosimilar
Biosimilar Pharmaceuticals - analysis
Carbohydrates
Chromatography, Liquid - methods
Clinical trials
Glycoconjugates - analysis
Glycosides - analysis
glycosylation
Humans
Immunoglobulins
Immunotherapy
Infliximab
Infliximab - analysis
Japan
Lysine
Lysine - analysis
Molecular Structure
Monoclonal antibodies
Papain
Tandem Mass Spectrometry - methods
time-of-flight MS
TNF inhibitors
Tumor necrosis factor-α
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Summary:Biosimilar products of therapeutic antibodies have been launched all over the world. They can relieve some of the economic burden of medicines. Although clinical trials have demonstrated the equivalency of biosimilar products with their reference product, biosimilar products are not commonly used in clinical practice. One reason is that the structural difference between the reference product and a biosimilar one remains unclear. We analyzed glycoforms and amino acids of an infliximab biosimilar product approved in Japan compared to that of the reference product (Remicade®). By combination of papain digestion and LC/ time-of-flight (TOF)-MS, we established a valuable method to analyze these therapeutic antibodies. Nine glycoforms were detected in infliximab, and a difference in amino acids was observed. In the glycoforms of MMF, MGnF/GnMF, GnGn, GnGnF, AGnF/GnAF, and AAF, the relative intensities were significantly different between the reference and biosimilar product. Furthermore, we elucidated that the content rate of the C-terminal lysine was different among glycoforms. In conclusion, our analytical method can analyze not only amino acids but also carbohydrate chains of therapeutic antibodies, and will provide a useful strategy to evaluate bio-medicines including biosimilar antibodies.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.b18-00491