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期 刊 ：中国中药杂志 2008年 33卷 19期 页码：2241.

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；

Keywords:aristolochic acid I, aristolochic acidⅡ, HPLC, plasma concentration, pharmacokinetics,

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0.056～56.3 mg·L^-1与峰面积比呈良好的线性关系(r=0.999 7)，样品平均回收率为88.7%，日内日间精密度的RSD均<8%。AAⅡ在0.192～11.52 mg·L^-1与峰面积比呈良好的线性关系(r=0.998 9)，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5 mg·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：t_1/2α(8.2±1.7) min，t_1/2β(79.6±28.5) min，CL(0.010±0.003) L·min^-1·kg^-1；AAⅡ的主要药动学参数为：t_1/2α(56.7±38.1) min，t_1/2β(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。

Abstract:Objective: To develop an HPLC method for determination of the plasma concentration of aristolochic acid Ⅰ (AAⅠ) and aristolochic acidⅡ (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, t_1/2α=(8.2±1.7) min, t_1/2β=(79.6±28.5) min for AAⅠ; CL=(0.003±0.001) L·min^-1·kg^-1, t_1/2α=(56.7±38.1) min, t_1/2β=(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 AAⅡ and Aristololactam-the metabolite of AAⅠ- were slower than that of AAⅠ.

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