Application of On-line SPE-HPLC System in Pharmacokinetic Study of Highly Active Anti-Cancer Compound TEB-415
10.11895/j.issn.0253-3820.140757
- VernacularTitle:在线固相萃取-高效液相色谱系统在高抗癌活性化合物TEB-415药代动力学中的应用
- Author:
Man WANG
;
Yabin WEN
;
Kangning LIU
;
Ge SI
;
Lei LIU
;
Zheng YIN
;
Yaxin LU
- Publication Type:Journal Article
- Keywords:
On-line solid phase extraction;
High performance liquid chromatography;
Tyrosine kinase inhibitors TEB-415;
Pharmacokinetics;
Blood drug level
- From:
Chinese Journal of Analytical Chemistry
2014;(12):1729-1734
- CountryChina
- Language:Chinese
-
Abstract:
An on-line solid phase extraction-high performance liquid chromatography ( SPE-HPLC ) system was applied in the plasma pharmacokinetic study of highly active anti-cancer compound tyrosine kinase inhibitors (TEB-415) in mouse. The on-line SPE-HPLC method associated with Ultimate3000 system which was applied to the determination of the blood drug level of TEB-415 in mouse plasma. C18 column ( Venusil MP, 150 mm × 4. 6 mm, 5μm) was used as analytical column and the mobile phase consisted of acetonitrile-5 mmol/L monopotassium phosphate buffer ( pH 3 . 5 ) at a flow rate of 1 . 0 mL/min was used as the isocratic elution. An MF Ph-1 column (10 mm×4 mm, 5 μm) was used as on-line SPE column, and water and water-acetonitrile were used as the washing solvent and elution solvent respectively. The detection wavelength was set at 262 nm. The pharmacokinetic parameters were calculated by WinNonlin 5. 2 software. The linear range of the calibration curve was between 100 and 20000 μg/L, and the limit of qualification was 20 μg/L. The extraction recovery was between 90 . 5% and 94 . 6%. The RSD of intra-day and inter-day precision was less than 3. 5%. The accuracy of short-term stability, freeze-thaw stability and long-term stability were between 91. 49% and 101. 96%. After oral medication, the mean peak time (Tmax) of TEB-415 in mice was 5. 29 h, and the mean maximum concentration ( Cmax) was 3403μg/L. The area under the curve ( AUC) of TEB-415 was 24600 μg/L·h. This drug's mean half-life was 3. 84 h, and its mean retention time (MRT) was 6. 56 h. These parameters suggested that TEB-415 had appropriate rate of absorption and elimination with preferable bioavailability.
