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. 2019 Dec 10:2019:5016757.
doi: 10.1155/2019/5016757. eCollection 2019.

Determination of Anlotinib, a Tyrosine Kinase Inhibitor, in Rat Plasma by UHPLC-MS/MS and Its Application to a Pharmacokinetic Study

Zhe Wang  1 , Le-Jing Lian  1 , Yan-Yan Dong  2 , Xiao Cui  1 , Jian-Chang Qian  3 , Cheng-Ke Huang  1 , Rui-Jie Chen  1 , Wei Sun  1
Affiliations

Determination of Anlotinib, a Tyrosine Kinase Inhibitor, in Rat Plasma by UHPLC-MS/MS and Its Application to a Pharmacokinetic Study

Zhe Wang et al. J Anal Methods Chem. .

Abstract

Anlotinib is a novel inhibitor of receptor kinase tyrosine with multitargets and has a broad spectrum of inhibitory action on tumor angiogenesis and growth. A simple and rapid UHPLC-MS/MS bioanalytical method was validated for the determination of anlotinib in rat plasma, using imatinib as an internal standard. An Acquity BEH C18 column was used to separate analytes. The eluents consisted of formic acid/water (0.1 : 100, v/v) and acetonitrile with a mobile phase. A triple quadrupole mass spectrometer was operated for the quantification with multiple reaction monitoring (MRM) to determine transitions: 408.2 ⟶ 339.1 for anlotinib, and 494.3 ⟶ 394.1 for imatinib. The validated range was 0.1-50 ng/mL for anlotinib. Mean recovery rate of anlotinib in plasma was ≥99.32% and reproducible. Also, the intra- and interday precisions were both below 15%. This robust method was successfully applied to support the pharmacokinetic study of anlotinib in rats.

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Conflict of interest statement

The authors declare no conflicts of interest in publication of this research.

Figures

Figure 1
Figure 1
Product ion mass spectra of anlotinib ([M+H]+ m/z 408.2 ⟶ 339.1) and imatinib ([M+H]+ m/z 494.3 ⟶ 394.1) in the positive ionization mode.
Figure 2
Figure 2
Representative MRM chromatograms of anlotinib and imatinib (IS) in rat plasma. (a) Blank samples from plasma (A); (b) sample at 40 ng/mL for anlotinib in plasma; (c) sample at 10 min after oral administration of 10 mg/kg anlotinib to rat.
Figure 3
Figure 3
The pharmacokinetic profiles of anlotinib after oral administration to rats (n = 6).
See this image and copyright information in PMC

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