Development of a Specific and Sensitive Enzyme-Linked Immunosorbent Assay for the Quantification of Imatinib

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概要

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• Imatinib is an oral tyrosine kinase inhibitor used for first-line treatment of chronic myeloid leukemia. Therapeutic drug monitoring targeting trough plasma levels of about 1000 ng/mL may help to optimize imantinib's therapeutic effect. This paper reports a specific and sensitive enzyme-linked immunosorbent assay (ELISA) for a pharmacokinetic evaluation of imatinib. Anti-imatinib antibody was obtained by immunizing rabbits with an antigen conjugated with bovine serum albumin and succinimidyl 4-{(4-methyl-1-piperazinyl)methyl}-benzoate. Enzyme labeling of imatinib with horseradish peroxidase was similarly performed using succinimidyl 4-{(4-methyl-1-piperazinyl)methyl}-benzoate. A simple ELISA for imatinib was developed using the principle of direct competition between imatinib and the enzyme marker for anti-imatinib antibody which had been adsorbed by the plastic surface of a microtiter plate. Serum imatinib concentrations lower than 40 pg/mL were reproducibly measurable using the ELISA. This ELISA was specific to imatinib and showed very slight cross-reactivity (1.2%) with a major metabolite, N-desmethyl imatinib. Using this assay, drug levels were easily measured in the blood of mice after their oral administration of imatinib at a single dose of 50 mg/kg. The specificity and sensitivity of the ELISA for imatinib should provide a valuable new tool for use in therapeutic drug monitoring and pharmacokinetic studies of imatinib.

• 公益社団法人 日本薬学会の論文

著者

• FUJITO Hiroshi

  Department of Pharmacy, Saga University Hospital

• Shin Masashi

  Applied Life Science Department, Faculty of Biotechnology and Life Science, Sojo University

• Saita Tetsuya

  Applied Life Science Department, Faculty of Biotechnology and Life Science, Sojo University

関連論文

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• Screening of Furanocoumarin Derivatives in Citrus Fruits by Enzyme-Linked Immunosorbent Assay(Analytical Biochemistry)
• Development of a Specific and Sensitive Enzyme-Linked Immunosorbent Assay for the Quantification of Imatinib
• Liquid Chromatographic Determination of Ethambutol in Serum Samples Based on Intramolecular Excimer-forming Fluorescence Derivatization

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