舒尼替尼药代动力学和脑肾组织分布特征

Pharmacokinetics and tissue distribution characteristics of sunitinib

目的:建立HPLC-UV法测定大鼠血浆和小鼠组织中舒尼替尼,研究舒尼替尼在大鼠体内药代动力学和小鼠脑肾组织分布特征。方法:采用蛋白沉淀法处理血浆和组织样品,Waters XBridgeTMC18(4.6 mm×250 mm,5μm)色谱柱,流动相为甲醇-0.02 mol/L磷酸二氢钠(70∶30);进样量:30μL;流速:1.0 mL/min;检测波长310nm;柱温:25℃。结果:舒尼替尼大鼠血浆浓度在0.0192~15.34μg/mL范围内,小鼠脑、肾组织浓度在0.0383~11.50和0.0383~69.00μg/mL范围内线性关系良好。大鼠口服灌服舒尼替尼20 mg/kg,Tmax=9.0 h,Cmax=0.194 mg/L,t1/2=18.4 h,AUC(0-∞)=6.8 mg·L^-1·h,绝对生物利用度为47.1%;舒尼替尼可以透过血脑屏障,但在脑组织中浓度较低,在肾组织中有较高浓度。结论:建立了大鼠血浆及小鼠组织中舒尼替尼的HPLC-UV测定方法,此方法简便、快速,结果准确可靠,为舒尼替尼的临床应用提供参考。

AIM:To establish a HPLC-UV method to determine sunitinib in rat plasma and mouse tissues,and to study its pharmacokinetics in rats and tissue distribution characteristics in mice.METH-ODS:The biotic samples were prepared by protein precipitation followed by a stereoselective analysis of sunitinib was achieved on Waters XBridgeTMC18(4.6 mm×250 mm,5μm)with a mobile phase composing of methanol-0.02 mol/L sodium dihydrogen phosphate(70∶30)at a flow rate of 1.0 mL/min.The detection wavelength was 310 nm,and the column temperature was 25℃.RESULTS:The calibration curve for rat plasma sunitinib was linear in the range of 0.0192-15.34μg/mL.The linear ranges in mice brain and kidney were 0.0383-11.50and 0.0383-69.00μg/mL,respectively.After intragastric administration of sunitinib at a dose of 20mg/kg to rats,the pharmacokinetic characteristics were Tmax=9.0 h,Cmax=0.194 mg/L,t1/2=18.4h,AUC(0-∞)=6.8 mg·L^-1·h.And the absolute bioavailablity was 47.1%.It was indicated that sunitinib could permeate the blood brain barrier,but the concentration was lower in brain and higher in kidney.CONCLUSION:A HPLC-UV method for the determination of sunitinib in rat plasma and mouse tissues was established.The method is simple,rapid,reliable,and provides a reference for the clinical application of sunitinib.