马兜铃酸Ⅰ,Ⅱ在大鼠体内的药动学研究  

Study of pharmacokinetics of aristolochic acid Ⅰ and Ⅱ in rats

作　　者：陈西敬[1] 卢琴[1] 方芳[1] 王广基[1] 

机构地区：[1]中国药科大学药代研究中心,江苏南京210009

出　　处：《中国中药杂志》2008年第19期2241-2244,共4页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(30472060)

摘　　要：目的：建立高效液相色谱法测定血浆中马兜铃酸Ⅰ（AAⅠ）和马兜铃酸Ⅱ（AAⅡ）浓度的方法，研究其在大鼠体内的药动学。方法：HPLC测定大鼠静脉注射AAI和Ⅱ后的血药浓度，并进行药动学分析。结果：AAⅠ在0．056～56．3mg·L^-1与峰面积比呈良好的线性关系（r=0．9997），样品平均回收率为88．7％，日内日问精密度的RSD均〈8％。AAⅡ在0．192—11．52mg·L^-1与峰面积比呈良好的线性关系（r=0．9989），样品平均回收率为85．8％，日内精密度的RSD〈3％，日间精密度的RSD小于10％。按5mg·kg^-1剂量尾静脉给予AAⅠ与AAⅡ混合物后，两者在大鼠体内的处置过程符合二房室模型，AAI的主要药动学参数为：t1/2α（8．2±1．7）min，t1/2β（79．6±28．5）min，CL（0．010±0．003）L·min^-2·kg6-1；AAⅡ的主要药动学参数为：t1／2α（56．7±38．1）min，t1／2β（209±37．9）min，CL（0．003±0．001）L·min^-1·kg^-1。结论：AAⅠ和AAⅡ的HPLC简单可靠，可用于两者的血药浓度分析及药动学研究。静注给药后AAⅠ与AAⅡ的血药浓度的变化速度有较大差异，前者的分布和消除相对较快而后者相对较慢。Objective： To develop an HPLC method for determination of the plasma concentration of aristolochic acid Ⅰ （ AAⅠ ） and aristolochic acid Ⅱ（ AAⅡ ） and study their pharmacokinetics in rats. Method： The plasma samples were extracted with acetonitrile. The analysis involved a C18 column as stationary phase and methanol, water and acetic acid as mobile phase. The flow rate was 1.0 mL·min^-1 , the UV detection wavelength was 315 nm. After a single intravenous dose of 5 mg· kg^-1 AA in rats, the pharmacokinetic parameters were estimated. Result： The calibration curve of AAⅠ was linear over the range from 0. 056 mg·L^-1 to 56. 3 mg· L^-1 with a correlation coefficient of 0. 999 7. The mean recovery rate was 88.7%. The RSD of within-day and between-day were all less than 8%. And the calibration curve of AAII was linear over the range from 0. 192 mg·L^-1 to 11.52 mg·L^-1 with a correlation coefficient of 0. 998 9. The mean recovery was 85. 8%. The RSD of within-day was less than 3% and between-day was less than 10%. The main pharmacokinetic parameters were estimated to be as follows： CL = （0. 010 ± 0. 003） L · min^-1· kg^-1, t1/2α = （8.2 ± 1.7） min, t1/2β = （79. 6 ±28.5） rain for AAⅠ ; CL = （0. 003 ±0. 001 ） L · min^-1· kg^-1, t1/2α= （56. 7 ±38.1 ）min, t1/2β = （ 209. 3 ± 37.9 ） min for AAⅡ. Conclusion： The established HPLC method is simple and sensitive to determine the concentration of AAⅠ , AAⅡ and the metabolite of AAⅠ in rat plasma. From the result of animal＇s test, we can find that AAⅠ was quickly eliminated from plasma, the elimination of AA Ⅱ and Aristololactam-the metabolite of AA Ⅰ - were slower than that of AA Ⅰ.

关 键 词：马兜铃酸Ⅰ 马兜铃酸Ⅱ 高效液相色谱法 血药浓度 药动学 

分 类 号：R285.5[医药卫生—中药学]