目的 利用固相萃取-高效液相色谱，建立测定人血浆中瑞格非尼及其代谢产物N-氧化瑞格非尼和去甲-N-氧化瑞格非尼的方法，研究其人体药动力学。方法 采用固相萃取-高效液相色谱法进行检测，以索拉非尼为内标，Oasis HLB型固相萃取柱（200 mg×6 mL）；流动相：0.5%磷酸二氢钾溶液-乙腈（30∶70）；检测波长：260 nm；体积流量：0.5 mL/min；柱温：30℃；进样量：5 μL。健康志愿者空腹条件下用50 mL温水送服40、160 mg/片瑞格非尼片。利用DAS 2.1.1软件对药-时数据进行统计学分析，并得到主要药动学数据。结果 瑞格非尼及其代谢产物N-氧化瑞格非尼和去甲-N-氧化瑞格非尼在10~10 000 ng/mL线性关系良好；检测限（LOD）分别为0.67、0.72、0.57 ng/mL；定量限（LOQ）分别为1.98、2.32、1.61 ng/mL；得到瑞格非尼及其代谢产物N-氧化瑞格非尼和去甲-N-氧化瑞格非尼药-时曲线和主要药动学数据。40、160 mg/片规格瑞格非尼片中瑞格非尼的C_max、AUC_last、AUC_mf、t_1/2分别为（2 215.7±216.9）、（5 721.2±672.1）ng/mL，（13 772.9±10 231.1）、（51 182.3±43 219.2）ng·h/mL，（12 858.3±12 510.2）、（66 531.8±51 093.1）ng·h/mL，（6.58±1.31）、（13.12±4.23）h。结论 采用固相萃取-高效液相色谱法考察瑞格非尼片在健康志愿者体内的药动学研究具有操作简便、可靠性高等优点，对该药的应用具有重要意义。

Objective To establish a method for simultaneous determination of regorafenib and its metabolites N-oxidemetabolite and desmethyl N-oxide metabolite in human plasma by solid phase extraction-HPLC, and study pharmacokinetics of Regorafenib Tablets in health volunteer. Methods After plasma sample was performed, using sorafenib as internal standard, the determination was performed on Oasis HLB column (200 mm×6 mm), with 0.5% monopotassium phosphate-methanol (30:70) as mobile phase, the UV detection wavelength was 260 nm with flow rate as 0.5 mL/min. The column temperature was set at 40℃, and injection volume was 5 μL. Health volunteer were po administered with Regorafenib Tablets 40 and 160 mg/tablet under fasting conditions with 50 mL warm water. DAS 2.1.1 software was used to calculate the major pharmacokinetic parameters. Results The linear ranges for regorafenib and its metabolites N-oxidemetabolite and desmethyl-N-oxide metabolite were 10-10 000 ng/mL. LOD and LOQ were 0.67, 0.72, 0.57 ng/mL and 1.98, 2.32, and 1.61 ng/mL. Plasma concentration-time curves and major pharmacokinetic parameters of regorafenib and its metabolites N-oxidemetabolite and desmethyl N-oxide metabolite were obtained. Main pharmacokinetic parameters of regorafenib in Regorafenib Tablets with 40 and 160 mg/tablet were as following:C_max were (2 215.7 ±216.9) and (5 721.2 ±672.1) ng/mL; AUClas were (13 772.9 ±10 231.1) and (51 182.3 ±43 219.2) ng·h/mL; AUC_mf were (12 858.3 ±12 510.2) and (66 531.8 ±51 093.1) ng·h/mL; t_1/2 were (6.58 ±1.31) and (13.12 ±4.23) ng·h/mL. Conclusion The method is rapid and repeatable, and can be used for the determination of plasma concentration and pharmacokinetic study for Regorafenib Tablets in health volunteer, which is of great significance to the application of the drug.