大鼠血浆中奥莫替尼浓度的检测及其药动学特征

Detection of olmutinib concentration in rat plasma and its pharmacokinetic characteristics

目的建立HPLC法测定大鼠血浆中奥莫替尼浓度并研究其在大鼠体内的药动学特征。方法血浆使用高氯酸沉淀,液相条件:ZORBAX SB-C18(150 mm×4. 6 mm,5μm)为色谱柱,流动相为水-乙腈-0. 1%三氟乙酸(60∶20∶20),流速为1. 0m L·min-1,检测波长为280 nm。10只SD大鼠经灌胃给药,分别给予50 mg·kg-1的奥莫替尼,在给药后的11个时间点采集大鼠的尾静脉血,测定血浆中奥莫替尼的浓度,使用DAS软件计算药动学参数。结果奥莫替尼在质量浓度0. 1～20 mg·L^(-1)时线性关系良好(r=0. 999 8),定量下限为0. 1 mg·L^(-1),日内和日间RSD均<10%,回收率> 80%。奥莫替尼在大鼠血浆中峰浓度ρmax为(11. 86±3. 4) mg·L^(-1),达峰时间tmax为(3. 3±0. 5) h,AUC0→t为(151±31) mg·h·L^(-1),AUC0→∞为(160±28) mg·h·L^(-1)。结论该方法测定准确可靠,简单快速,适合奥莫替尼的血药浓度测定。奥莫替尼在大鼠体内的药动学符合二室模型。

AIM To develop a high performance liquid chromatography method for the determination of ol- mutinib in rat plasma and study its pharmacokinetic characteristics. METHODS The plasma was precipitated with perehlorie acid. The liquid phase conditions were as follows： ZORBAX SB-C18 （150 mm· 4.6 mm, 5 μm） as chromatographic column, mobile phase of water-acetonitrile - 0.1% trifluoroacetic acid （ 60： 20： 20 ） , flow rate of 1.0 mL ~ min-land detection wavelength of 280 nm. Totally 10 SD rats were administrated by intragastrie adminis- tration and treated with olmutinib 50 mg · kg- 1. The tail vein blood of rats was taken in the 11 time points after ad- ministration, the concentration of olmutinib was determined, and the pharmacokinetie parameters were calculated by DAS software. RESULTS Olmutinib in the range of 0.1 -20 mg · L^-1 was in a good linear relationship（r= 0. 999 8）. The limit of quantitation was 0.1 mg · L- 1. The RSDs of intra-day and inter-day were both less than 10% , and the recovery was more than 80%. Olmutinib peak concentration ρmax= in rat plasma was（ 11.86±3.4） mg·L-1, tmax= was （3.3±0.5）h,AUC0→t was（151 ±31） mg · h · L-1 ,and AUC0→t. was（160±28） mg · h · L-1. CONCLUSION This method is accurate, reliable, simple and rapid, and suitable for the determination of concentration of olmutinib in rat plasma. The pharmacokinetics of olmutinib in rats conforms to the two compartment model.