LC-MS法测定Beagle犬血浆中苦参碱及其药代动力学  

Pharmacokinetics of matrine in Beagle dogs by LC-MS

作　　者：王素军[1] 王广基[1] 李晓天[1] 马仁玲[2] 盛龙生[2] 孙建国[1] 谢海棠[1] 

机构地区：[1]中国药科大学药物代谢研究中心 [2]中国药科大学分析测试中心

出　　处：《中国临床药理学与治疗学》2004年第12期1361-1364,共4页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家 8 63计划基金项目 (№ 2 0 0 3AA2Z3 47A ) ;国际合作项目(№BZ2 0 0 40 42 ) ;江苏省药物代谢动力学重点实验室项目(№BM2 0 0 12 0 1)

摘　　要：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LichrospherC18柱 ,2 5 0mm× 4 .6mm (ID) ,5 μm,柱温 :2 5℃ ;流动相 :10mmol·L-1醋酸胺水溶液 甲醇 (2 5 75 ) ,流速 :1ml·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 2 4 9.2。结果 :苦参碱在 2～ 5 0 0 0 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 .3μg·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 ,Cmax 为 382 1±70 5 μg·L-1,Tmax为 0 .4± 0 .1h ,T1 2 β为 11.2± 2 .1h ,AUC0→∝ 为 74 46± 14 5 6 μg·h·L-1,绝对生物利用度为(6 0 .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。AIM: To establish LC-MS method in the de te rmination of matrine in plasma of Beagle dogs and to investigate its absolute bi oavailability. METHODS: Lichrospher C18 column was used as the a nalytical column and maintained at 25 ℃, 250 mm× 4.6 mm (ID), and 5 μm. The mobile phase was consisted of 10 mmol·L -1 ammonium ace tate 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 mor e than 96.6%. The disposition was conformed to a two- compartment model. Th e C max, T max, T 1/2β, AUC 0→∝ and absolute bioavailabil ity 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)%, resp ectively. CONCLUSION: This study provides a highly sensitive, ra pid, simple and special method for determining concentra tions of matrine in plasma of Beagle dogs. Matrine shows higher absolute bioavai lability in Beagle dogs.

关 键 词：苦参碱 药代动力学 液相色谱/质谱联用 BEAGLE犬 绝对生物利用度 

分 类 号：R969.1[医药卫生—药理学]