氧化苦参碱在犬体内的药动学

Pharmacokinetics of oxymatrine in beagle dogs

目的:建立beagle犬血浆中氧化苦参碱的LCMS测定法,测定其灌胃后在beagle犬体内的药动学。方法:采用LichrospherC18柱(250mm×4.6mm,5μm),柱温:25℃。流动相为10mmol·L-1醋酸铵水溶液甲醇(25∶75),流速:1mL·min-1;电喷雾离子化(ESI)方式,采用选择性离子检测法,检测离子为正离子,氧化苦参碱的离子为[m/z+H]+265.1,内标非那雄胺的离子是[m/z+H]+373.3。结果:氧化苦参碱在2～5000μg·L-1的范围内呈良好的线性关系(r=0.9990),最低检出限达0.6μg·L-1,日内和日间误差均小于4.2%,萃取回收率大于90%;氧化苦参碱的药时数据符合二室模型,Cmax为(2418.3±970.8)μg·L-1,tmax为(1.0±0.3)h,t1/2β为(5.5±1.6)h,AUC0→∝为(6117.4±1080.2)μg·L-1·h。结论:该法灵敏、简单,专属性强,可用于犬血浆中氧化苦参碱的测定。

OBJECTIVE To establish I.C-MS method in the determination of oxymatrine in plasma and investigate its pharmacokinetics in beagle dogs. METHODS Lichrospher C18 column was used as the analytical column maintained at 25℃ （250 mm×4. 6 mm, 5μm）. The mobile phase consisted of 10 mmol·L^-1 CH3 COONH4-CH3 OH （25 ： 75）. Flow rate was 1 mL·min^-1. Electrospray ionization（ESI）was carried out. The ESI ion source was set in positive ion polasity mode. The selective ion monitoring （SIM）was set at m/z 265. 1 for oxymatrine. RESULTS The linearity of oxymatrine ranged from 2 to 5000 μg·L^-1 （r=0. 9990）. The detection limits of oxymatrine was 0. 6μg·L-^-1， The RSD（ % ） of within day and between day was less than 4. 2%. The recovery was more than 90%. The disposition was conformed to a two-compartment model. The Cmax, T12β, AUC0-∞of oxymatrine were（2 418.3±971）.8）μg·L^-1, （1.0±0.3） h,（5.5±1.6） h,（6 117.42±1 081）.2）μg·L^-1.h. CONCLUSION This method is highly sensitive, rapid, simple and specific enough for determining concentrations of oxymatrine in plasma of beagle dogs.