title: Development of a specific and sensitive enzyme-linked immunosorbent assay for the quantification of imatinib.
abstract: 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.
authors.affiliation: Applied Life Science Department, Faculty of Biotechnology and Life Science, Sojo University.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Saita
authors.forename: Masashi
authors.initials: M
authors.lastname: Shin
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujito
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001549:Benzamides / Q000032:analysis* / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics; D016903:Drug Monitoring; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006735:Horseradish Peroxidase / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D051379:Mice; D008807:Mice, Inbred BALB C; D010879:Piperazines / Q000032:analysis* / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics; D047428:Protein Kinase Inhibitors / Q000032:analysis* / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000032:analysis* / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics; D011817:Rabbits; D012680:Sensitivity and Specificity; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D000906:Antibodies; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012710:Serum Albumin, Bovine; D000068877:Imatinib Mesylate; D006735:Horseradish Peroxidase