Investigation of Pharmacokinetics of Surufatinib in Rats by UPLC-MS/MS
Objective To establish an ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS/MS)method for determining the concentration of surufatinib in rat plasma.Methods The plasma sample was treated with precipitated protein before injection with carbamazepine as the internal standard.The chromatographic column was Waters Acquity UPLC® BEH C18 column(50 mm × 2.1 mm,1.7 μm),the mobile phase was formic acid-ammonia-water(1∶1∶1 000,V/V/V)-acetonitrile(gradient elution),the flow rate was 0.4 mL/min,the column temperature was 40 ℃,and the injection volume was 1 μL.Electric spray ionization(ESI)was adopted with the positive ion and multi-reaction monitoring mode,the air curtain pressure was 35 psi,the atomization pressure was 30 psi,and the spray voltage was 5 500 V.The ion to mass-charge-ratio(m/z)was m/z 481.2 → 329.0 for surufatinib,and m/z 237.2 → 194.0 for carbamazepine.Results The retention times of surufatinib and carbamazepine were 0.93 min and 0.94 min,respectively.The linear range of surufatinib was 0.1-500 ng/mL(r=0.997 2,n=9).The results of precision,stability,accuracy,and matrix effect tests all met the requirements.The lower limit of quantification was 0.1 ng/mL.After a single oral administration of 2 mg/kg body weight,the peak time(tmax)was about 1.33 h,the peak concentration(Cmax)was about 5.92 ng/mL,the half-life(t1/2)was about 5.31 h,and the average residence time(MRT)was about 4.02 h.The concentration of surufatinib in liver was 201.2 ng/mL at 4 h after administration,which was much higher than 3.57 ng/mL in plasma.Conclusion This method is simple,rapid,accurate,and sensitive,which can be used for rapid determination of the concentration of surufatinib in rat plasma.Surufatinib is prone to accumulate in the liver.
万方数据
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