目的 研究羌活提取物中羌活醇在大鼠体内的药代动力学规律.方法 羌活醇分别以60、30和15 mg·kg-1剂量大鼠灌胃给药,给药后于不同时间点采血,血浆样品经乙腈处理后,用高效液相色谱(HPLC)-荧光法测定血药浓度,色谱柱:Spherisorb 10 ODS(1)(250 mm×4.6 mm);流动相:甲醇-乙腈-0.025 mol·L-1磷酸三乙胺溶液(15∶45∶40);流速:1 mL·min-1;检测波长:EM=480 nm.不同时间点的数据采用DAS 2.0药代动力学软件拟合处理,计算该药的药代动力学参数,分析羌活醇在体内药代动力学特点.结果 血浆样品中,羌活醇的线性范围为1.164×10-4～1.164×10-2 mg·mL-1(r=0.997);各血药浓度的提取回收率均大于80%,日内或日间精密度实验RSD＜4%,血浆中回收率＞90%.经DAS 2.0药代动力学软件进行自动拟合处理不同时间点的药物血浆浓度,药物药代动力学参数显示:高、中、低3个剂量组(分别为11.64×10-3、5.82×10-3、1.164×10-3 mg·mL-1 的血浆样品)中,羌活醇的平均高峰血药浓度(Cmax)分别为(5.243±3.116)、(1.892±0.888)、(0.764±0.120)mg·L-1,血药浓度-时间面积(AUC)(0-∞)相应分别为(32.658±31.202)、(17.511±2.287)、(3.246±2.432)mg·L-1·h-1,说明随着药物剂量的增加,Cmax与AUC也相应的增加.羌活醇高、中、低3个剂量组消除半衰竭(T1/2z)分别为(3.184±1.959)、(3.207±3.036)、(3.013±3.225)h,表明剂量不同,其T1/2z差异无统计学意义(P>0.05).结论 利用HPLC-荧光法对中药羌活中羌活醇进行药代动力学研究,方法稳定、灵敏度高、专属性强.药代动力学试验显示药物在动物体内吸收、消除较快,代谢迅速,所得结果可为下一步新药试验研究提供参考.%Objective To study the pharmacokineties of rhizoma extract notopterol in rats. Methods Blood sampling was performed at different time points after intragastric administration of notopterol (15,30 and 60 mg · kg-1) to rats. Plasma notopterol concentrations were deter-mined by high-performance liquid chromatography (HPLC) after protein precipitation with aceto-nitrile. The analytes were separated on a Spherisorb 10 ODS(l)column (250 mm×4. 6 mm) with a mobile phase consisting of methanol-acetonitrile-0. 025 mol · L-1 triethylamine phosphate (15 : 45 : 40). The flow rate was 1 mL · min-1 and the eluent was detected at 480 nm. The pharmaco-kinefic parameters were calculated by DAS 2. 0. Results The linear range of notopterol in plasma was 1.164×10- 4 ~ 1. 164×10 -2 mg · mL-1 (r -0. 997) and the recovery rate was more than 80%. Intra and inter-days precision and accuracy RSD were less than 4% and the obtained recov-ery rate was more than 90 %. Pharmacokinetic parameters were as follows: Cmax was (5. 243 ± 3. 116) ,(1. 892 ± 0. 888) and (0. 764 ±0. 120) mg · L-1AUC (0-∞) was (32. 658 ±31. 202), (17. 511 ± 2.287) and (3.246 ± 2.432) mg · L-1 · h-1,and T1/2Z was (3. 184 ± 1. 959), (3. 207 ± 3. 036) and (3. 013 ± 3. 225) hours in 60,30 and 15 mg · kg Notopterol treatment groups,respec-tively. Excellent linearity was obtained between notopterol doses and AUC. No significant differ-ences were found in T12z among the three doses of notopterol(P>0. 05). Conclusion The HPLC-fluorescence method is stable, sensitive and specific for determining the concentrations of no-topterol in rat plasma. Pharmacokinetic trial showed that notopterol underwent absorption, rapid elimination of rapid metabolism in rats. These results can provide a reference for the next new drug trial research.
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