title: Simultaneous determination of nintedanib and its metabolite by UPLC-MS/MS in rat plasma and its application to a pharmacokinetic study.
abstract: To establish a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of concentration of nintedanib and its metabolite BIBF 1202 in rat plasma. The nintedanib and its metabolite and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1 mm×50 mm, 1.7 μm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.30 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z540.3→113.1 for nintedanib, m/z526.3→113.0 for BIBF 1202 and m/z285.3→193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated for 1.0-200 ng/mL for nintedanib and 0.5-100 ng/mL for BIBF 1202 using 100 μL of plasma sample. Total time for each chromatograph was 3.0 min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD) <10.8% and the accuracy values ranged from -11.9% to 10.4%. The method was successfully applied to a pharmacokinetic study of nintedanib and BIBF 1202 in rats after oral administration of nintedanib.
authors.affiliation: Department of Forensic Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, PR China; School of Pharmacy of Wenzhou Medical University, Wenzhou 325035, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Lin
authors.affiliation: The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, PR China.
authors.forename: Li-man
authors.initials: LM
authors.lastname: Qiao
authors.affiliation: Medical College of Henan University of Science and Technology, Luoyang 471003, PR China.
authors.forename: Yu-niao
authors.initials: YN
authors.lastname: Zhang
authors.affiliation: Medical College of Henan University of Science and Technology, Luoyang 471003, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Forensic Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: lxins@mail.xjtu.edu.cn.
authors.forename: Xin-she
authors.initials: XS
authors.lastname: Liu
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D007211:Indoles / Q000097:blood* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D007211:Indoles; C530716:nintedanib
keywords: BIBF 1202; Nintedanib; Pharmacokinetics; Plasma; UPLC–MS/MS