Application of liquid chromatography–tandem mass spectrometry to study the effect of docetaxel on pharmacokinetics and tissue distribution of apatinib in mice

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2018-04, Vol.1083, p.198-203
• Main Authors: Feng, Siqi, Zhang, Jingwei, Wang, Ying, Sun, Runbin, Feng, Dong, Peng, Ying, Yang, Na, Zhang, Yue, Gao, Haoxue, Gu, Huilin, Wang, Guangji, Aa, Jiye, Zhou, Fang
• Format: Article
• Language: English
• Subjects: Animals; Apatinib; Chromatography, Liquid - methods; Docetaxel; LC-MS/MS; Linear Models; Male; Mice; Mice, Inbred BALB C; Pharmacokinetics; Pyridines - analysis; Pyridines - pharmacokinetics; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry - methods; Taxoids - analysis; Taxoids - pharmacokinetics; Tissue Distribution
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2018.03.017

Apatinib, a highly selective small-molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), has attracted many attentions due to its anticancer activity in various malignancies containing non-small-cell lung cancer (NSCLC). Our previous preclinical study confirmed the enhanced anti-tumor efficacy of combined treatment between apatinib and docetaxel for NSCLC. However, the effects of docetaxel on pharmacokinetics and tissue distribution of apatinib are not clear. In present study, a reliable HPLC-MS/MS method was established for determination of apatinib. This method had a good linearity in the range of 1–5000 ng/mL, and the recovery and matrix effect were 100.1–103.5%, 77.6–83.5%, respectively. Plasma exposure level of apatinib and the values of Cmax, AUC0–12h, T1/2, and MRT were not affected by multi-dose of docetaxel. The tissue distributions (kidney, heart, lung, spleen) of apatinib in combined treatment group were lower at 0.25 h but higher at 2 h, and that in intestine and liver were not significantly changed compared with control group. However, pre-treatment with docetaxel had no significant effect on AUC0–4h of apatinib in tissues in mice. In conclusion, plasma and tissues exposure levels of apatinib were not affected by long-termed treatment with docetaxel, indicating that docetaxel is less likely to increase the side effect of apatinib such as hypertension, hand-foot syndrome and so on. •Development of a rapid and sensitive HPLC-MS/MS method for the detection of apatinib.•The limit of quantification is reduced much lower to 1 ng/mL.•Application of the method in pharmacokinetics and tissue distribution of apatinib.•Pharmacokinetics and tissue distribution of apatinib were not impacted by docetaxel.