摘要
应用在线固相萃取( SPE)-高效液相色谱( HPLC)方法研究TEB-415在小鼠体内的药代动力学。通过在线SPE-HPLC方法结合Ultimate3000系统测定TEB-415血药浓度,使用 Venusil MP C18分析柱(150 mm ×4.6 mm,5μm),乙腈-5mmol/L磷酸盐缓冲液(pH 3.5)为流动相,流速1.0 mL/min,等度洗脱; Capcell MF Ph-1为在线SPE柱(10 mm×mm,5μm),水为淋洗液,洗脱剂为水-乙腈,检测波长262 nm。采用WinNonlin5.2软件计算药代动力学参数。血浆中 TEB-415测定的线性范围为100~20000μg/L,定量限( S/N≥10)为20.0μg/L,提取回收率为90.5%~94.6%,日内与日间精密度RSD均小于3.5%,短期稳定性、冻融稳定性及长期稳定性准确度为91.49%~101.96%。 TEB-415口服给药后,在小鼠体内平均达峰时间tmax为5.29 h,平均药峰浓度Cmax为3403μg/L, TEB-415的0~t时间段药时曲线下面积AUC值为AUC0-t=24600μg/L·h,平均半衰期t1/2=3.84 h,体内平均滞留时间MRT =6.56 h,呈现吸收速度适中、吸收程度较高、体内消除速度适中的药代动力学特点。
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 Uhimate3000 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, 5 μm) 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-clay 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 3403 μg/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.
出处
《分析化学》
SCIE
EI
CAS
CSCD
北大核心
2014年第12期1729-1734,共6页
Chinese Journal of Analytical Chemistry
基金
天津市自然科学基金(No.12JCQNJC08500)资助项目~~
关键词
在线固相萃取
高效液相色谱
TEB-415
药代动力学
血药浓度
On-line solid phase extraction
High performance liquid chromatography
Tyrosine kinaseinhibitors TEB-415
Pharmacokinetics
Blood drug level