新型钙离子拮抗剂DY-9836在大鼠体内的药动学

Study on pharmacokinetics of a new type calcium antagonist DY-9836 in rats

目的建立测定大鼠血浆中新型钙离子拮抗剂DY-9836浓度的高效液相色谱-荧光检测(HPLCFl)法,研究DY-9836在大鼠体内的药动学。方法以维拉帕米为内标,色谱柱:Extend C18(4.6 mm×150 mm,5μm);流动相:乙酸钠(pH=6.5)-乙腈(50∶50,V/V);流速:1 mL·min-1;柱温:35℃;λex=304 nm,λem=335 nm。大鼠灌胃后,测定血浆中DY-9836的浓度,采用WinNonLin 5.2软件计算药动学参数。结果 DY-9836的血药浓度线性范围为0.327～4.083μg·mL-1;方法回收率分别为93.35%～98.08%;DY-9836在大鼠体内的主要药动学参数:Ke为(0.05±0.01)h-1、t1/2为(14.20±0.92)h、tmax为(1.25±0.42)h、ρmax为(2.98±0.56)μg·mL-1、AUC0-t为(37.74±2.00)μg·h·mL-1、AUC0-∞为(41.71±1.90)μg·h·mL-1、CL为(480.3±22.0)mL·h-1·kg-1、MRT0-t为(19.30±0.60)h。结论本实验所建立的测定血浆中DY-9836的HPLC-Fl方法简便、快速、灵敏、准确、可靠。

AIM To establish a high performance liquid chromatography- fluorescence method for the determination of calcium antagonist DY- 9836 concentration in rats plasma and to study the pharmacokinetics parameters. METHODS Chromatographic column was Extend Cls column （4.6 mm × 150 mm, 5 μm） with 35 ℃ of column temperature. The mobile phase was sodium acetate-acetonitrile （50 ： 50, V/V） with a flow rate of 1.0 mL·min^-1 under the condition of pH6.5. A fluorescence detector was set at λex 304 nm and λem335 nm,the internal standard was verapamil. After intragastric administration, the plasma concentrations of DY-9836 in rats were determined and the pharmaeokinetie parameters were calculated by Win Non Lin 5.2 software. RESULTS A good linearity was obtained over the range of 0.327 - 4.083μg·mL^-1 and the extraction recovery of this method ranged from 93.35% to 98.08%. The main pharmacokinetic parameters of DY-9836 were as follows： Ke （0.05 ±0.01） h^-1, tla （14.20 ＋ 0.92） h, t-max （1.25 ± 0.42） h, ρ_max （2.98 ± 0.56） μg·mL^-1, AUC0-∞（37.74 ± 2.0） μg·h·mL^-1, AUC0-∞ （41.71 ± 1.9） μg·h·mL^-1, CL （480.3± 22） mL·h·mL^-1, MRT0-t（19.30 ±0.60） h.CONCLUSION The method established in this paper was simple, sensitive, exclusive and reliable.