论文部分内容阅读
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。
Objective : To establish a LC-MS method for determination of matrine in Beagle dogs plasma and determine its pharmacokinetics and absolute bioavailability. METHODS: Lichrospher C18 column, 250 mm×4.6 mm (ID), 5 μm, column temperature: 25°C; mobile phase: 10 mmol·L-1 aqueous solution of acetic acid in methanol (25 75), flow rate: 1 ml·min -1. In electrospray ionization (ESI) mode, using selective ion detection, the detected ions were positive ions, and the matrine ions were [M + H] + , m z 2 4 9.2. RESULTS: The matrine ranged from 2 to 500 μg·L-1 and showed a good linear relationship (r=0.9975). The detection limit was 0.3 μg·L-1. The intra-day and inter-day errors were all less than 4.5%, and the method recovery was greater than 96.6%. The drug-time data was in a two-compartment model with a Cmax of 382 1±70 5 μg·L-1 and a Tmax of 0.4±0. At 1 h, T1 2 β was 11.2±2.1 h, AUC0→∝ was 74 46±14 5 6 μg·h·L-1, and absolute bioavailability was (6 0.1 ± 19.0)%. Conclusion : This method is sensitive, rapid, simple, and highly specific. Matrine has high absolute bioavailability in Beagle dogs.