title: A high-performance liquid chromatography-mass spectrometry assay for quantitation of the tyrosine kinase inhibitor nilotinib in human plasma and serum.
abstract: Nilotinib (AMN-107, Tasigna) is a small-molecule inhibitor of BCR/ABL, approved for chronic myelogenous leukemia. We developed and validated, according to FDA-guidelines, an LC-MS assay for sensitive, accurate and precise quantitation of nilotinib in 0.2 mL human plasma or serum. After acetonitrile protein precipitation, separation is achieved with a hydro-Synergi column and a 0.1% formic acid in methanol/water-gradient. Detection uses electrospray, positive-mode ionization mass spectrometry. Between 5 (LLOQ) and 5000 ng/mL, accuracy (92.1-109.5%), intra-assay precision (2.5-7.8%), and inter-assay precision (0-5.6%)) were within FDA limits. We demonstrated the suitability of this assay by quantitating plasma concentrations of nilotinib in a healthy volunteer after oral administration of 400 mg nilotinib.
authors.affiliation: Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA 15213, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Parise
authors.forename: Merrill J
authors.initials: MJ
authors.lastname: Egorin
authors.forename: Susan M
authors.initials: SM
authors.lastname: Christner
authors.forename: Dhvani D
authors.initials: DD
authors.lastname: Shah
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Jan H
authors.initials: JH
authors.lastname: Beumer
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D008297:Male; D047428:Protein Kinase Inhibitors / Q000097:blood* / Q000737:chemistry; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000097:blood* / Q000737:chemistry; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011505:Protein-Tyrosine Kinases; C498826:nilotinib