HPLC-MS法测定Beagle犬血浆中氧化苦参碱及其药代动力学

目的: 建立Beagle犬血浆中氧化苦参碱的LC-MS测定法,测定它的绝对生物利用度。方法: Beagle犬6只,随机分为2组,采用单剂量双周期自身交叉设计,分别给犬单剂量静脉注射或灌胃氧化苦参碱,用LC-MS法测定给药后的血浆中药物浓度。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 %,方法回收率大于96.7 %;氧化苦参碱的药-时数据符合二室模型,C_max为2.42±0.97μg·L^-1,T_max为1.0±0.3 h,T_1/2β为5.54±1.58h,AUC_0→∝为6.12±1.08μg·L^-1·h^-1,绝对生物利用度为(19.4±9.01)%。结论: 该法灵敏、简单,专属性强;氧化苦参碱在Beagle犬体内绝对生物利用度较低。

Pharmacokinetics of oxymatrine in Beagle dogs by LC-MS

AIM: To establish LC-MS method in determination of oxymatrine in plasma of Beagle dogs and to investigate its absolute bioavailability.METHODS: According to a randomized two-period crossover design, the Beagle dogs were iv 6 mg·kg^-1 and ig 30 mg·kg^-1 of oxymatrine, respectively.Drug concentration in plasma was assayed by HPLC ESI MS. RESULTS: The linearity of oxymatrine ranged from 2 to 5 000 μg·L^-1(r=0.9990).The detection limits of oxymatrine was 0.6μg·L^-1 .The values of RSD of within day and between day were less than 4.2 %.The recovery of this method was more than 96.7 %.The disposition was conformed to a two-compartment model .The C_max, T_max, T_1/2β, AUC_0→∝ and absolute bioavailability of oxymatrine were 2.42±0.97μg·L^-1,1.0±0.3h,5.54±1.58h,6.12±1.08μg·L^-1·h^-1 and (19.4±9.0)%, respectively.CONCLUSION: This study provides a simple, reliable and special method for determining concentrations of oxymatrine in plasma of Beagle dog.Oxymatrine shows low absolute bioavailability in Beagle dogs.