盐酸关附甲素代谢产物关附壬素的药动学研究

目的建立测定盐酸关附壬素血药浓度的液相色谱-质谱联用分析方法(LCMS),并探讨其在大鼠体内的药动学。方法大鼠iv盐酸关附壬素20mg·kg-1后不同时间点采血,利用LCMS法测定血药浓度,并用3P87软件求算其药代动力学参数。结果盐酸关附壬素浓度在005~20mg·L-1范围内线性关系良好(r=09994)。绝对回收率大于80%,日内、日间RSD均小于15%。大鼠iv关附壬素20mg·kg-1后其主要动力学参数AUC、Vc、T1/2、CLs分别为1570mg·h-1·L-1、131L·kg-1、249h、146L·kg-1·h-1。排泄试验结果表明,给药24h后从尿中,胆汁中和粪便中排出的原形药物累计量相当于给药量的706%、91%、53%。结论该法具有专属性强,灵敏度高,可用于关附壬素的体内定量分析。

Studies on pharmacokinetics of guanfu base I,a metabolite of guanfu base A

Aim To establish an analytical method for determination of guanfu base I (GFI) concentration in plasma and investigate its pharmacokinetics in rats. Methods Rats were given a 20 mg·kg~-1 dose intravenously. Blood samples were collected at various times after iv administration. The plasma concentration of GFI was determined by LC-MS. Pharmacokinetic parameters were calculated by 3p97 program.Results The method was linear in the 0.05～20 mg·L~-1 concentration range (r=~0.999 4 ). The recovery of guanfu base I was more than 80%.The intraday and interday precision, expressed as the relative standard deviation (RSD), was generally good (<15%). The major pharmacokinetic parameters AUC, Vc, T_~1/2 , CLs were:15.70 mg·h~-1 ·L~-1 , 1.31 L·kg~-1 , 2.49 h, 1.46 L·kg~-1 ·h~-1 respectively. After iv administration 24 h,excretion of GFI in rat urine、bile、faece were 70.6%, 9.1%, 5.3% respectively.Conclusion The method described in this report has high sensitivity and specificity, and was suitable for pharmacokinetic studies of GFI.