液相色谱-质谱联用法测定犬血浆中盐酸关附甲素的血药浓度及其药代动力学  

DETERMINATION OF GUANFU BASE A HYDROCHLORIDE IN PLASMA BY LC-MS METHOD AND ITS PHARMACOKINETICS IN DOGS

作　　者：吴民淑[1] 王广基[1] 蔡晓辉[1] 孙建国[1] 刘静涵[2] 

机构地区：[1]中国药科大学药代研究中心,江苏南京210009 [2]中国药科大学植化教研室,江苏南京210009

出　　处：《药学学报》2002年第7期551-554,共4页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金 ( 39970 86 2 );国家 973项目(G9980 5 1119)

摘　　要：目的　建立用于测定盐酸关附甲素血药浓度的液相色谱 质谱联用分析方法 ,并探讨关附甲素在犬体内的药代动力学。方法　犬 6只iv盐酸关附甲素 7 5 6mg·kg- 1 后采集一系列血样 ,利用LC MS联用系统测定血浆药物浓度 ,并用 3P87软件拟合求算药代动力学参数。结果　盐酸关附甲素浓度 0 42～ 2 1 2 μg·mL- 1 线性关系良好 (γ=0 9994)。绝对回收率高于 80 % ,日内、日间RSD均小于 15 % ,符合生物样品分析要求。 6只犬iv盐酸关附甲素7 5 6mg·kg- 1 后的血药浓度 时间曲线符合开放三室模型 ,其快分布相、慢分布相和末端消除相的半衰期 (T1 2 π ,T1 2 α和T1 2 β)分别为 0 0 7,1 5和 13 5h。曲线下面积 (AUC)、中央室分布容积 (Vc)和血浆清除率 (CLs)分别为 6 1 43μg·h·mL- 1 ,0 37L·kg- 1 和 0 14L·kg- 1 ·h- 1 。结论　建立的LC MS联用方法专属性强 ,灵敏度高 ,可用于盐酸关附甲素的体内定量分析。AIM To establish an analytical method for determination of guanfu base A (GFA) concentration in plasma and to study its pharmacokinetic profile in dogs. METHODS Six dogs were given a 7.56 mg·kg -1 dose intravenously. Blood samples were collected at various time-points after drug administration. Analytical method based on liquid chromatography-mass spectrometry (LC-MS) was established to determine the plasma concentration of GFA. Pharmacokinetic evaluation was carried out using the 3P87 program. RESULTS The calibration curves were linear over the concentration range from 0.42 μg·mL -1 to 21.2 μg·mL -1 (γ=0.9994). The intra-day and inter-day precisions were generally good (<15%) at low, medium and high concentrations. The overall recovery of the analytes was more than 80%. Six dogs were given an iv dose of 7.56 mg·kg -1 of GFA hydrochloride, an open three compartment model best described the concentration-time profiles for GFA. The half-lives for the rapid and slow distribution phase and terminal elimination phase (T 1/2 π, T 1/2 α and T 1/2 β) were 0.07 h, 1.5 h, and 13.5 h, respectively. The total area under the plasma concentration-time curve (AUC), the volume of the central compartment (V c), and plasma clearance (CL s) were 61.43 μg·h·mL -1 , 0.37 L·kg -1 and 0.14 L·kg -1 ·h -1 , respectively. CONCLUSION The analytical method was shown to be sensitive, specific, rapid and reproducible, and was suitable for pharmacokinetic studies of GFA.

关 键 词：液相色谱-质谱联用法 盐酸关附甲素 血药浓度 药代动力学 

分 类 号：R285[医药卫生—中药学]