CAJ | 학술논문

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×4 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。
응용재선고상췌취( SPE)-고효액상색보( HPLC)방법연구TEB-415재소서체내적약대동역학。통과재선SPE-HPLC방법결합Ultimate3000계통측정TEB-415혈약농도,사용 Venusil MP C18분석주(150 mm ×4.6 mm,5μm),을정-5mmol/L린산염완충액(pH 3.5)위류동상,류속1.0 mL/min,등도세탈； Capcell MF Ph-1위재선SPE주(10 mm×4 mm,5μm),수위림세액,세탈제위수-을정,검측파장262 nm。채용WinNonlin5.2연건계산약대동역학삼수。혈장중 TEB-415측정적선성범위위100~20000μg/L,정량한( S/N≥10)위20.0μg/L,제취회수솔위90.5％~94.6％,일내여일간정밀도RSD균소우3.5％,단기은정성、동융은정성급장기은정성준학도위91.49％~101.96％。 TEB-415구복급약후,재소서체내평균체봉시간tmax위5.29 h,평균약봉농도Cmax위3403μg/L, TEB-415적0~t시간단약시곡선하면적AUC치위AUC0-t=24600μg/L·h,평균반쇠기t1/2=3.84 h,체내평균체류시간MRT =6.56 h,정현흡수속도괄중、흡수정도교고、체내소제속도괄중적약대동역학특점。
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.