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  2. Quantitative analysis of tivantinib in rat plasma using ultra performance liquid chromatography with tandem mass spectrometry

Quantitative analysis of tivantinib in rat plasma using ultra performance liquid chromatography with tandem mass spectrometry

  • J Pharm Biomed Anal. 2016 Jul 15;126:98-102. doi: 10.1016/j.jpba.2016.05.003.
Yan-Li Bai 1 Hong-Chang Yuan 2 Dong-Tao Zhang 3 Yuan Liu 3 Yin Zhang 3
Affiliations

Affiliations

  • 1 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.
  • 2 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, 611137 Chengdu, PR China.
  • 3 Medical College of Henan University of Science and Technology, 471003 Luoyang, PR China.
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.

Keywords

Pharmacokinetics; Plasma; Rat; Tivantinib; UPLC–MS/MS.

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