【摘要】 目的建立以高效液相色谱法测定大鼠血浆中厄洛替尼浓度的方法,并研究其在大鼠体内的药物动力学。方法色谱柱为Dikma Diamonsil C18,流动相为乙腈-水=60∶40(pH=2.0),流速为1.2 mL.min-1,柱温为35℃;检测波长331nm。结果厄洛替尼血药浓度在80～4 000ng.mL-1与峰面积线性关系良好(r=0.997 7),最低检测限为80ng.mL-1;日内、日间RSD均≤10%,提取回收率在83.77%～85.68%。6只SD大鼠单剂量静脉给予厄洛替尼(10mg.kg-1)后药动学参数分别为:Cmax=(1.203×103±118.2)ng.mL-1;t1/2=(23.24±2.33)h;AUC0-t=(4.713×103±213.6)ng.h.mL-1;AUC0-∞=(5.363×103±323.6)ng.h.mL-1;MRT=(25.91±2.34)h;Vd=(28.44±1.58)L。结论本方法简便、准确、灵敏、专属性强,同样适用于人血浆中厄洛替尼浓度的测定及其药动学研究,对于评价厄洛替尼疗效和安全性有重要意义。更多还原

【Abstract】 Objective To develop a simple and sensitive HPLC method to determine the content of erlotinib in rat plasma. Methods The chromatographic separation was carried out on a Dikma Diamonsil C18 column with the mobile phase consisting of acetonitrile-water(60∶40,v/v,pH=2.0) at 1.2 mL·min-1.The column temperature was 35 ℃.The detection wavelength was 331 nm. Results The calibration was linear at 80-4 000 ng·mL-1 for erlotinib.The inter-and intra-day RSDs were less than 10%.The pharmacokinetic parameters were:Cmax(1 203.12±118.23) ng·mL-1;t1/2(23.24±2.33)h;AUC0-t(4 713.25±213.55)ng·h·mL-1;AUC0-∞(5 363.38±323.62)ng·h·mL-1;MRT(25.91±2.34)h;Vd(28.44±1.58)L. Conclusion This method is simple,sensitive and accurate,which can be used in routine clinical practice to monitor erlotinib concentration in the plasma from non-small cell lung cancer patients.更多还原