【摘要】 目的　探讨左旋黄皮酰胺 [(- )clau]及其主要代谢产物 6 OH clau在大鼠体内的药代动力学。方法　建立了RP HPLC UV法。固定相为Kromasil 10 0C18(5 μm)色谱柱 ,流动相为乙腈—甲醇—水 (2 1∶16 5∶6 2 5 ) ,DM 9384作内标 ,氯仿作提取溶剂。结果　测得 (- )clau的回收率为 96 91%～ 10 5 74% ,日内、日间RSD低于 7% ,最低检测浓度为 2 4ng·mL-1,(- )clau和 6 OH clau分别在 0 0 47～ 96 8μg·mL-1和 0 0 49～ 2 0 0 μg·mL-1,线性关系良好 (γ =0 999) ;(- )clau和 6 OH clau血浆浓度 时间曲线符合二室开放模型 ,同时求得两者的药代动力学参数。结论　数据表明 (- )clau在大鼠血浆中的分布、代谢转化和消除均较快更多还原

【Abstract】 AIM To Determine the concentration of (-) clausenamide[(-)clau] and its essential metabolite─6 Hydroxyl clausenamide(6 OH clau) in rat plasma and study their pharmacokinetics.METHODS A reversed phase high performance liquid chromatography with ultraviolet detection has been developed for determination of (-)clau and its metabolites in rat plasma using a column of Kromasil C 18 (5 μm) and mobile phase of acetonitrile methanol water(21∶16 5∶62 5). DM 9384 was used as an internal standard. Rat plasma samples were extracted with chloroform. RESULTS The mean relative recovery of (-)clau was 100 9%±4 4%( n =3) with within day precision of 1 8%～6 2% and between day precision of 1 06%～3 31%, and the limit of detection was 24 ng·mL -1 . At the range of 0 47～968 μg·mL -1 for (-)clau, and 0 049～200 μg·mL -1 for 6 OH clau, there was a linear relationship with a value for γ=0 999. By the nonlinear least squares regression and F test between different compartments using a computer program 3P87, the plasma concentration vs time course of (-) clau given iv 80 mg·kg -1 to rats was found to fit a 2 compartments open model. The following pharmacokinetic parameters were obtained: for (-)clau, T 1/2 α=(12 19±1 68) min, V d=(1 19±0 31) L·kg -1 , T 1/2 β=(156 65±18 65) min and AUC 0～720 =(1286 09±171 56) min·μg·L -1 ; for 6 OH(-)clau, T 1/2 Kt=(9 61±3 56) min, T 1/2 β=(238 81±48 66) min, T max=(17 91±3 05) min, C max=(1 29±0 11) μg·mL -1 and AUC 0～480 =(78 31±5 35) min·μg·L -1 . CONCLUSION (-)Clau exhibited a pharmacokinetic character that its distribution, transformation and elimination in rat plasma are all relatively rapid.更多还原