title: Quantitative analysis of tivantinib in rat plasma using ultra performance liquid chromatography with tandem mass spectrometry.
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 tivantinib in rat plasma. Plasma samples were processed with a protein precipitation. The separation was achieved by an Acquity UPLC BEH C18 (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 1.0-100ng/mL (r(2)>0.9967) with a lower limit of quantification (1.0ng/mL). The extraction recovery was in the range of 79.4-84.2% for tivantinib and 80.3% for carbamazepine (internal standard, IS). The intra- and inter-day precision was below 8.9% and accuracy was from -7.2% to 9.5%. No notable matrix effect and astaticism was observed for tivantinib. The method has been successfully applied to a pharmacokinetic study of tivantinib in rats for the first time, which provides the basis for the further development and application of tivantinib.
authors.affiliation: The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, 471003 Luoyang, PR China. Electronic address: yifuyuanbyl@126.com.
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Bai
authors.affiliation: School of Pharmacy, Chengdu University of Traditional Chinese Medicine, 611137 Chengdu, PR China.
authors.forename: Hong-Chang
authors.initials: HC
authors.lastname: Yuan
authors.affiliation: Medical College of Henan University of Science and Technology, 471003 Luoyang, PR China.
authors.forename: Dong-Tao
authors.initials: DT
authors.lastname: Zhang
authors.affiliation: Medical College of Henan University of Science and Technology, 471003 Luoyang, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Medical College of Henan University of Science and Technology, 471003 Luoyang, PR China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D057230:Limit of Detection; D008297:Male; D011760:Pyrrolidinones / Q000032:analysis / Q000097:blood*; D011804:Quinolines / Q000032:analysis / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C551661:ARQ 197; D000970:Antineoplastic Agents; D011760:Pyrrolidinones; D011804:Quinolines
keywords: Pharmacokinetics; Plasma; Rat; Tivantinib; UPLC–MS/MS