LC-MS法测定盐酸维拉帕米缓释微球在大鼠体内的药动学行为

Study on pharmacokinetics of vera pammy hydrochloride sustained release microspheres in rats by LC-MS

目的制备盐酸维拉帕米缓释微球,应用液质联用法研究其在大鼠体内的药动学行为。方法应用喷雾干燥法制备维拉帕米缓释微球,分别灌胃给予大鼠维拉帕米缓释微球和市售普通片剂。大鼠血浆用甲醇萃取,以草酸艾司西酞普兰为内标物,采用液质联用法测定其血药质量浓度,采用PK-Solver软件计算其药动学参数。结果盐酸维拉帕米缓释微球在0.5、1、2、4、7、10、12和24 h的体外累积释放度分别为22.52%、32.35%、41.77%、55.32%、68.70%、72.10%、75.17%和78.25%。普通片剂的t_(max)、ρ_(max)、AUC0-∞分别为(1.3±0.4)μg·h·L^(-1)、(447.7±50.6)μg·h·L^(-1)和(1 482.6±81.2)μg·h·L^(-1),缓释微球的t_(max)、ρ_(max)、AUC0-∞分别为(4.1±1.6)μg·h·L^(-1)、(152.1±20.4)μg·h·L^(-1)和(1 478.1±89.7)μg·h·L^(-1)。结论以喷雾干燥法制备的盐酸维拉帕米(verapamil hydrochlorid,Ver)缓释微球体外释药性能良好,在体实验表明缓释微球能显著的降低给药后血药质量浓度的峰谷现象,延长药物作用时间并且具有良好的生物等效性。

Objective To prepare vera pammy hydrochloride sustained-release microspheres and study its pharmacokinetics in rats. Methods Vera pammy sustained release microspheres were prepared by spray drying method. The rats were treated with vera pammy sustained release microspheres and commercially available tablets. The plasma is extracted with methanol and the concentrations of blood were determined by HPLCMS/MS method. The pharmacokinetic parameters were calculated by PK-Solver. Results The release rate of sustained release microspheres is 22. 52%,32. 35%,41. 77%,55. 32%,68. 70%,72. 10%,75. 17% and78. 25% at 0. 5,1,2,4,7,10,12 and 24 h respectively. The common tablets tmax,ρmax and AUC0-∞ were（ 1. 3 ± 0. 4） h,（ 447. 7 ± 50. 6） μg·h·L^-1 and（ 1 482. 6 ± 81. 2） μg·h·L^-1 respectively, sustained releasemicrospheres tmax,ρmax and AUC0-∞ to infinity（ 4. 1 ± 1. 6） h,（ 152. 1 ± 20. 4） μg·h·L^-1 and（ 1 478. 1 ±89. 7） μg·h·L^-1. Conclusions The release rate of vera pammy sustained-release microspheres prepared by spray drying method is good in vitro. The experimental results show that the sustained-release microspheres can significantly reduce blood drug concentration fluctuation and prolong the action time. It have good biological equivalence.