title: A simple method for the determination of Bosutinib in rat plasma by UPLC-MS/MS.
abstract: In this work, a simple, sensitive and fast ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitative determination of bosutinib in rat plasma. Plasma samples were processed with a protein precipitation. The separation was achieved by an Acquity UPLC BEH C18 column (2.1mm×50mm, 1.7μm) column with a gradient mobile phase consisting of 0.1% formic acid in water and acetonitrile. Detection was carried out using positive-ion electrospray tandem mass spectrometry via multiple reaction monitoring (MRM). The validated method had an excellent linearity in the range of 0.1-500ng/mL (R(2)>0.9977) with a lower limit of quantification (0.1ng/mL). The extraction recovery was in the range of 75.6-85.6% for bosutinib and 81.2% for pirfenidone (internal standard, IS). The intra- and inter-day precision was below 9.7% and accuracy was from -8.1% to 8.8%. No notable matrix effect and astaticism was observed for bosutinib. The method has been successfully applied to a pharmacokinetic study of bosutinib in rats for the first time, which provides the basis for the further development and application of bosutinib.
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Xu
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Xin-ce
authors.initials: XC
authors.lastname: Huang
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Dai
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: zmt0417@hotmail.com.
authors.forename: Meng-tao
authors.initials: MT
authors.lastname: Zhou
mesh_terms: D000814:Aniline Compounds / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D057230:Limit of Detection; D009570:Nitriles / Q000097:blood* / Q000493:pharmacokinetics; D011804:Quinolines / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000814:Aniline Compounds; D009570:Nitriles; D011804:Quinolines; C471992:bosutinib
keywords: Bosutinib; Pharmacokinetics; Plasma; Rat; UPLC-MS/MS