Application of On-line SPE-HPLC System in Pharmacokinetic Study of Highly Active Anti-cancer Compound TEB-415

作者：Wang Man; Wen Ya-Bin; Liu Kang-Ning; Si Ge; Liu Lei; Yin Zheng; Lu Ya-Xin^*

来源：Chinese Journal of Analytical Chemistry, 2014, 42(12): 1729-1733.

DOI：10.1016/S1872-2040(14)60786-6

• Online solid phase extraction
• High performance liquid chromatography
• Tyrosine kinase inhibitors TEB-415
• Pharmacokinetics
• Blood drug level

An on-line solid phase extraction-high performance liquid chromatography (SPE-HPLC) system was developed for the plasma pharmacokinetic study of highly active anti-cancer compound TEB-415 in mouse. A C-18 column (Venusil MP, 100 mm x 4.6 mm, 5 mu m) was used as the analytical column and a mixed solution of acetonitrile-5 mM monopotassium phosphate buffer (pH 3.5) at a flow rate of 1.0 mL min(-1) as the mobile phase for the isocratic elution. The on-line solid phase extraction was carried out on an MF Ph-1 column (10 mm x 4 mm, 5 mu m) with purified water as the washing solvent and 5 mM monopotassium phosphate buffer (pH 3.5) as the elution solvent. The detected wavelength was set at 262 nm. The pharmacokinetic parameters were calculated by WinNonlin 5.2 software. The linear range of TEB-415 was 100-20000 mu g L-1 with a limit of qualification of 20 mu g L-1. The extraction recovery was 91.99%-99.14% and the RSD of intra-and inter-day precision was less than 3.5%. The accuracy of short-term stability, freeze-thaw stability and long-term stability were 91.5%-101.5%. After oral medication, the mean peak time (T-max) of TEB-415 in mice was 5.29 h and the mean maximum concentration (C-max) was 3403 mu g L-1. The area under the curve (AUC) of TEB-415 was 24600 mu g L-1 h(-1). The mean half-life of drug in mice was 3.84 h, and the mean retention time (MRT) was 6.56 h. These parameters above suggest that TEB-415 has an appropriate rate of absorption and elimination for the mice. Meanwhile, it had preferable bioavailability.

• 出版日期2014-12
• 单位南开大学