title: Preparation of Antibodies and Development of an Enzyme-Linked Immunosorbent Assay for the Tyrosine Kinase Inhibitors Lapatinib and Nilotinib.
abstract: In this paper, we describe the production of the first specific antibodies against the tyrosine kinase inhibitors lapatinib and nilotinib. Anti-lapatinib antibody was obtained by immunizing rabbits with an antigen conjugated with bovine serum albumin using 3-chloro-4-((3-fluorobenzyl)oxy)aniline. Anti-nilotinib antibody was produced by immunizing mice with an antigen conjugated with bovine serum albumin using 2-(5-amino-2-methylanilino)-4-(3-pyridyl)pyrimidine. The generated antibodies were used to develop highly sensitive and specific enzyme-linked immunosorbent assays (ELISAs) for lapatinib and nilotinib in human serum. The assays were capable of detecting lapatinib and nilotinib at serum concentrations as low as 40 and 8 ng/mL, respectively. Using the two ELISAs, drugs levels were easily measured in the serum of rats after a single dose oral administration of lapatinib or nilotinib. The assays are therefore expected be valuable tools for therapeutic drug monitoring in the clinical setting and pharmacokinetic studies of lapatinib and nilotinib.
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: Yuta
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Masashi
authors.initials: M
authors.lastname: Shin
authors.forename: Yukitaka
authors.initials: Y
authors.lastname: Nakano
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D016903:Drug Monitoring; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006735:Horseradish Peroxidase; D006801:Humans; D000077341:Lapatinib; D008297:Male; D047428:Protein Kinase Inhibitors / Q000097:blood / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000097:blood / Q000276:immunology*; D011799:Quinazolines / Q000097:blood / Q000276:immunology*; D011817:Rabbits; D017208:Rats, Wistar
chemical_list: D000906:Antibodies; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011799:Quinazolines; D000077341:Lapatinib; D006735:Horseradish Peroxidase; D011505:Protein-Tyrosine Kinases; C498826:nilotinib