LC-MS 法测定Beagle 犬血浆中苦参碱及其药代动力学

目的: 建立Beagle 犬血浆中苦参碱的LC-MS测定法, 测定其药物动力学及绝对生物利用度。方法: 采用Lichrospher C18 柱, 250 mm×4.6 mm(ID),5 μm, 柱温:25 ℃;流动相:10 mmol·L^-1醋酸胺水溶液∶甲醇(25 ∶75), 流速:1 ml·min^-1 。电喷雾离子化(ESI) 方式, 采用选择性离子检测, 检测离子为正离子, 苦参碱的离子是M+H] +, m/z 249.2 。结果: 苦参碱在2～5 000 μg·L^-1的范围内呈良好的线性关系(r=0.9975), 最低检出限达0.3 μg·L^-1。日内和日间误差均小于4.5 %, 方法回收率大于96.6 %;药-时数据符合二室模型, C_max 为3821±705 μg·L^-1, T_max为0.4±0.1 h, T_1/2β为11.2±2.1 h,AUC_0→∞为7446±1456 μg·h·L^-1, 绝对生物利用度为(60.1±19.0) %。结论: 该法灵敏、快速、简单, 专属性强, 苦参碱在Beagle 犬体内有较高的绝对生物利用度。

Pharmacokinetics of matrine in Beagle dogs by LC-MS

AIM: To establish LC-MS method in the determination of matrine in plasma of Beagle dogs and to investigate its absolute bioavailability.METHODS: Lichrospher C18 column was used as the analytical column and maintained at 25 ℃, 250 mm×4.6 mm (ID), and 5 μm.The mobile phase was consisted of 10 mmol·L^-1ammonium acetate and methanol (25 ∶75, v ∶v).Flow rate was 1 ml·min^-1.Electrospray ionization (ESI) was carried out.The ESI ion source was set in positive ion polarity mode.The selective ion monitoring (SIM) was set at m z 249.2 for matrine.RESULTS: The linearity of matrine ranged from 2 to 5 000 μg·L^-1(r=0.9975) and the detection limits of it was 0.3 μg·L^-1.The RSD of within day and between day was less than 4.5 %.The recovery of this method was more than 96.6 %.The disposition was conformed to a two-compartment model.The C_max, T_max, T_1/2β, AUC_0→∞ and absolute bioavailability of matrine were 3821±705 μg·L^-1, 0.4±0.1 h, 11.2±2.1 h, 7446±1456 μg·L^-1·h and (60.1±19.0) %, respectively.CONCLUSION: This study provides a highly sensitive, rapid, simple and special method for determining concentrations of matrine in plasma of Beagle dogs.Matrine shows higher absolute bioavailability in Beagle dogs.