LC-MS/MS法测定大鼠血浆中吴茱萸碱的浓度及其药代动力学研究

目的：建立用于测定吴茱萸碱血药浓度的液相色谱-串联质谱联用分析方法,并研究吴茱萸碱在大鼠体内的药代动力学。方法：6只大鼠灌胃给药吴茱萸碱100mg/kg,眼底取血,LC-MS/MS法测定血药浓度,并用DAS药代动力学程序拟合计算药代动力学参数。结果：吴茱萸碱浓度在0.2～50ng/mL内,线性关系良好（r^2=0.9997）。提取回收率96.12%～99.46%,日内、日间RSD分别为4.61%～13.51%和5.65%～11.49%。主要药代动力学参数为：Cmax=（5.3±1.5）ng/mL;tmax=（22±8）min;t1/2=（451±176）min。结论：建立的LC-MS/MS方法专属性强,灵敏度高,可用于吴茱萸碱的体内定量分析。

Determination of evodiamine by high performance liquid chromatography-tandem mass spectrometry and pharmacokinetic studies in rats

AIM: To establish an LC-MS/MS method for determination of evodiamine concentration in rat plasma and to study its pharmacokinetic profile in rats. METHODS: Six rats were administrated (i.g.) evodiamine at the dose of 100 mg/kg. Blood samples were collected from eye socket. Evodiamine concentration in rat plasma was determined by LC-MS/MS method. The pharmacokinetic parameters were calculated using DAS program. RESULTS: A good linear relationship was obtained in the concentration range (0.2-50.0 ng/mL) studied (r2=0.9997). Average recoveries ranged from 96.12% to 99.46%. Intra-and inter-day relative standard deviations were 4.61%-13.51% and 5.65%-11.49%, respectively. The main pharmacokinetic parameters of evodiamine were as follows: Cmax (5.3±1.5) ng/mL; tmax (22±8) min; t1/2 (451±176) min. CONCLUSION: A selective and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the quantification of evodiamine in rat plasma is developed and validated. This method is successfully applied for the pharmacokinetic studies of evodiamine in rats.