論文

査読有り
2017年5月

An ultra-specific and sensitive sandwich ELISA for imatinib using two anti-imatinib antibodies

ANALYTICA CHIMICA ACTA
  • Tetsuya Saita
  • ,
  • Yuta Yamamoto
  • ,
  • Kazuhisa Hosoya
  • ,
  • Yutaro Yamamoto
  • ,
  • Sakiko Kimura
  • ,
  • Yutaka Narisawa
  • ,
  • Masashi Shin

969
開始ページ
72
終了ページ
78
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.aca.2017.03.034
出版者・発行元
ELSEVIER SCIENCE BV

The development of an immunoassay for a low-molecular-weight drug first requires the identification of specific antibodies that do not cross-react with the drug's metabolites. If two antibodies can simultaneously recognize the entire structure of the drug, we can then utilize them to establish an ultra-specific sandwich ELISA, free from interference due to the metabolic products of the drug. This paper reports an ultra-specific and sensitive sandwich ELISA for determination of the tyrosine kinase inhibitor imatinib using two anti-imatinib antibodies. The anti-imatinib antibodies were obtained by two partial structures of imatinib as haptens (2-(5-amino-2-methylanilino)-4-(3-pyridyl) pyrimidine and 4-{(4-methyl-1piperazinyl)- methyl}-benzoate). Under optimized conditions, this sandwich ELISA shows a linear detection range from 64 pg mL(-1) to 8 ng mL(-1), and a limit of detection of approximately 64 pg mL(-1) for 100-mu L samples. The ELISA is specific to imatinib and while there was no cross-reactivity with the major metabolite N-desmethyl-imatinib, slight cross-reactivity was found with metabolite pyridine-N-oxideimatinib. This assay demonstrated significantly lower cross-reactivity with metabolites than competitive ELISAs. Using this assay, drug levels were easily measured in rat blood after oral administration of imatinib via a single dose of 30 mg kg(-1) or 100 mg kg(-1). The levels in rat serum measured by this ELISA were comparable with those measured by HPLC, and there was a strong correlation between the values determined by the two methods (y = 0.983x + 0.081, R-2 = 0.948). Thus, we have successfully developed the first specific and sensitive sandwich ELISA for imatinib using two anti-imatinib antibodies. This sandwich ELISA will be a valuable tool for therapeutic drug monitoring and pharmacokinetic studies of imatinib. (C) 2017 Elsevier B.V. All rights reserved.

Web of Science ® 被引用回数 : 13

リンク情報
DOI
https://doi.org/10.1016/j.aca.2017.03.034
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28411632
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000399331500009&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.aca.2017.03.034
  • ISSN : 0003-2670
  • eISSN : 1873-4324
  • PubMed ID : 28411632
  • Web of Science ID : WOS:000399331500009

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