Simultaneous determination of nintedanib and its metabolite BIBF 1202 in different tissues of mice by UPLC-MS/MS and its application in drug tissue distribution study.
A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to simultaneous determine nintedanib and BIBF 1202 in mice plasma and tissue using carbamazepine as the internal standard (IS). Sample preparation was accomplished through a protein precipitation procedure with acetonitrile. The analyte and IS were separated on an Acquity UPLC BEH C18 column (2.1mm×50mm, 1.7μm) with the mobile phase of acetonitrile and 0.1% formic acid in water with gradient elution at a flow rate of 0.40mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) by multiple reactions monitoring (MRM) of the transitions at m/z 540.3→113.1 for nintedanib, m/z 526.3→113.1 for BIBF 1202 and m/z 237.1→194.1 for IS, respectively. The linearity of this method was found to be within the concentration range of 1-1000ng/mL with a lower limit of quantification of 1.0ng/mL for each drug. Only 3.0min was needed for an analytical run. The inter-day and intra-day precision and accuracy of quality control (QC) samples, evaluated both in plasma and tissue homogenates, were all within 15%. The method was successfully applied to the pharmacokinetic and tissue distribution study of nintedanib and BIBF 1202 in mice after oral administration of nintedanib.
Luoyang Central Hospital Affiliated to Zhengzhou University, 471003 Luoyang, PR China.
Xiao-wei
XW
Xu
Luoyang Central Hospital Affiliated to Zhengzhou University, 471003 Luoyang, PR China.
Xin-juan
XJ
Su
Medical College of Henan University of Science and Technology, 471003 Luoyang, PR China.
Yu-niao
YN
Zhang
Medical College of Henan University of Science and Technology, 471003 Luoyang, PR China.
Xiao-kang
XK
Zheng
Medical College of Henan University of Science and Technology, 471003 Luoyang, PR China.
Peng-fei
PF
Lv
Luoyang Central Hospital Affiliated to Zhengzhou University, 471003 Luoyang, PR China. Electronic address: lyhujie@163.com.
Jie
J
Hu
D000818:Animals; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics*; D007211:Indoles / Q000493:pharmacokinetics*; D051379:Mice; D014018:Tissue Distribution
D004791:Enzyme Inhibitors; D007211:Indoles; C530716:nintedanib
BIBF 1202; Nintedanib; Pharmacokinetics; Plasma; Tissue distribution; UPLC–MS/MS