吴民淑, 王广基, 蔡晓辉, 孙建国, 刘静涵. 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J. 药学学报, 2002, 37(7): 551-554.
引用本文: 吴民淑, 王广基, 蔡晓辉, 孙建国, 刘静涵. 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J. 药学学报, 2002, 37(7): 551-554.
WU Min-shu, WANG Guang-ji, CAI Xiao-hui, SUN Jian-guo, LIU Jing-han. DETERMINATION OF GUANFU BASE A HYDROCHLORIDE IN PLASMA BY LC-MS METHOD AND ITS PHARMACOKINETICS IN DOGSJ. Acta Pharmaceutica Sinica, 2002, 37(7): 551-554.
Citation: WU Min-shu, WANG Guang-ji, CAI Xiao-hui, SUN Jian-guo, LIU Jing-han. DETERMINATION OF GUANFU BASE A HYDROCHLORIDE IN PLASMA BY LC-MS METHOD AND ITS PHARMACOKINETICS IN DOGSJ. Acta Pharmaceutica Sinica, 2002, 37(7): 551-554.

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

  • 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7.56 mg·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0.42~21.2 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7.56 mg·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(t1/2π,t1/2α和t1/2β)分别为0.07,1.5和13.5 h。曲线下面积(AUC)、中央室分布容积(Vc)和血浆清除率(CLs)分别为61.43 μg·h·mL-1,0.37 L·kg-1和0.14 L·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。

     

    Abstract: AIMTo establish an analytical method for determination of guanfu base A (GFA) concentration in plasma and to study its pharmacokinetic profile in dogs. METHODSSix 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. RESULTSThe 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 (t1/2π, t1/2α and t1/2β) 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 (Vc), and plasma clearance (CLs) were 61.43 μg·h·mL-1, 0.37 L·kg-1 and 0.14 L·kg-1·h-1, respectively. CONCLUSIONThe analytical method was shown to be sensitive, specific, rapid and reproducible, and was suitable for pharmacokinetic studies of GFA.

     

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