延胡索提取物在大鼠血浆中的药代动力学研究

Pharmacokinetics Study of Corydalis Extracts in Rat Plasma

目的:考察延胡索提取物中主要成分延胡索乙素(tetrahydropalmatine,THP)和延胡索甲素(corydaline,CDL)在大鼠体内的药代动力学过程。方法:采用血药浓度法,LC-MS/MS测定大鼠ig不同浓度(0.46,0.93,1.38 g.kg-1)延胡索提取物后不同时间点的血药浓度,Win Nonlin药动学数据处理软件计算药动学参数。结果:ESI(+)离子化条件下采用MRM工作模式用m/z 370～354,m/z 356～340分别检测CDL、THP,同时以m/z 306～140来检测内标盐酸山莨菪碱(anisodaminehydrochlo-ride,ADM)。CDL,THP分别在1.13～565,1.5～750 ng.mL-1表现出良好的线性关系,高、中、低3个剂量的回收率、日内和日间精密度均符合要求,不同剂量THP和CDL的Cmax分别为(84.3±9.2),(157.3±99.6),(497.1±71.3)ng.mL-1和(30.8±1.3),(54.4±22.7),(91.2±15.4)ng.mL-1,Tmax分别为(54.8±6.9),(119.2±5.7),(62.5±7.5)min和(31.5±0.07),(65.6±10.6),(111.5±4.2)min。结论:LC-MS/MS选择性好,灵敏度高,适用于血浆样品成分含量的测定,为进一步的复方药代动力学的研究奠定了基础。

Objective：To investigate pharmacokinetics process of the major components of the extract Corydalis tetrahydropalmatine（tetrahydropalmatine,THP） and d-corydaline（corydaline,CDL） in rats.Method：U-sing LC-MS /MS to measure plasma concentration at different time after ig administration concentration of Corydalis extracts was determined,WinNonlin software was used to calculate pharmacokinetic parameters.Result：ESI（＋）i-ons under the condition of using MRM mode with m /z370-354,m /z 356-340 was used to detecte CDL,THP,while the m /z 306-140 was used to detect the internal standard anisodamine（anisodaminehydrochloride,ADM）.In the range of 1.13-565,1.5-750 ng.mL-1,CDL,THP showed good linearity,high,medium and low recovery rates of THP,and CDL,day and inter-day precision met the demands of quantification,Cmax were（84.3 ± 9.2）,（157.3 ± 99.6）,（497.1 ± 71.3）ng.mL-1 and（30.8 ± 1.3）,（54.4 ± 22.7）,（91.2 ± 15.4） ng.mL-1,Tmax were（54.8 ± 6.9）,（119.2 ± 5.7）,（62.5 ± 7.5） min and（31.5 ± 0.07）,（65.6 ± 10.6）,（111.5 ± 4.2）min.Conclusion： LC-MS /MS had good selectivity,high sensitivity for the determination of plasma sample.