Determination of nilotinib in human plasma by LC-MS/MS and its pharmacokinetic study
Objective:An LC-MS/MS method was established for the determination of nilotinib in human plasma,which was further applied to the pharmacokinetic study of nilotinib capsules in Chinese healthy subjects under fasting state.Methods:Deuterated nilotinib was used as the internal standard,and plasma samples were precipitated by methanol to separate proteins and centrifuged for supernatant injection.A Kinetex C18 column(100 mm×2.1 mm,2.6 μm)was applied using mobile phase A of water(containing 0.1%formic acid and 5 mmol·L-1 ammonium formate)and B of methanol with67%B was injected at a flow rate of 0.4mL·min-1.The ion pairs are 530.25→289.30 and 536.25→295.30 for nilotinib and internal standard,respectively.After full validation,the method was applied to a pharmacokinetic study in 12 fasted Chinese healthy subjects.Results:Good linearity was achieved for nilotinib in the concentration range of 2～600 ng·mL-1.The recoveries were within 97.0%～104.3%,and intra-and inter-day RSDs were below 4.18%and 6.43%,respectively.No significant matrix effects were observed in normal blank plasma.The hemolyzed and hyperlipidemic plasma sample were made by adding 5%whole blood and 2%intralipid into normal blank plasma,respectively.The results indicated that hemolyzed and hyperlipidemic matrix did not affect the accuracy of the assay.After oral administration of nilotinib capsules in 12 fasted Chinese healthy subjects,t1/2 was(24.7±32.2)h,Cmax was(400.1±164.6)ng·mL-1,Tmax was(2.4±0.9)h,AUC0→72 was(7 900±2 598)ng·mL-1·h,AUC0→∞ was(9 226±3 649)ng·mL-1·h.Conclusion:This method is rapid and sensitive,highly accurate,and suitable for the determination of plasma concentrations of nilotinib and further pharmacokinetic studies.
NETL
NSTL
万方数据
维普
