不同剂量尼奥宁的大鼠体内药动学研究

Study on the pharmacokinetics of neoline at different doses in rats

目的：研究不同给药剂量下尼奥宁在大鼠体内的药动学特征。方法：UPLC-Q-TOF-MS法分析灌胃（ig）给与低、中、高（1,2和4 mg·kg^-1）剂量的尼奥宁。采用Acquity UPLC BEH C18色谱柱进行分离,流动相为甲醇和0.1%甲酸水溶液（60∶40,v/v）,质谱采用ESI离子源和正离子监测方式测定大鼠血浆尼奥宁浓度。结果：低、中、高剂量的Cmax分别为（59.88±10.78）,（113.13±15.03）以及（182.60±15.27）ng·mL^-1,t1/2分别为（367.64±32.67）,（374.70±22.39）和（329.23±22.32）min,AUC0-∞分别为（21 863.17±3 952.21）,（47 546.41±10 319.239）和（63 806.88±13 387.34）ng·mL^-1·min。结论：尼奥宁在SD大鼠体内药动学特征符合一级动力学特征,AUC0-∞与剂量呈正相关,不同剂量尼奥宁体内消除率和消除方式类似。

Objective： To investigate the pharmacokinetics of neoline in rat plasma after oral administration of different dosages. Methods： UHPLC-Q-TOF-MS method was adopted to determine the plasma concentration of neoline after oral administration at 1,2,and 4 mg·kg^- 1. The analyte was separated on an Acquity UPLC BEH C18 column eluted with mobile phase consisting of methanol and 0. 1% formic acid aqueous solution（ 60 ∶ 40,v / v）.Electrospray ionization source was applied and operated in the positive ion mode. Results： The main pharmacokinetic parameters of neoline at three doses were as below： t1 /2（ 367. 64 ± 32. 67）,（ 374. 70 ± 22. 39）,and（ 329. 23 ± 22. 32） min; Cmax（ 59. 88 ± 10. 78）,（ 113. 13 ± 15. 03）,and（ 182. 60 ± 15. 27） ng·mL^- 1; AUC0 - ∞（ 21 863. 17 ± 3 952. 21）,（ 47 546. 41 ± 10 319. 239）,and（ 63 806. 88 ± 13 387. 34） ng·mL^- 1·min. Conclusion： The pharmacokinetics of neoline in rats conforms to first-order kinetics. The AUC0 - ∞is positively related with dosage,and the elimination rate and elimination way are similar for different doses of neoline.