附子中乌头类生物碱在大鼠体内的药动学研究

 目的 建立微透析取样技术结合 RP-HPLC 分析方法同步研究附子中主要有效成分乌头碱、次乌头碱和新乌头碱在大鼠体内的药动学过程。 方法 大鼠十二指肠给予附子提取物 1 055 mg·kg^-1 ，颈静脉微透析采样， RP-HPLC 测定透析液中乌头碱、次乌头碱和新乌头碱的含量，以回收率校正实际药物浓度，并用 3P97 程序计算药动学参数。 结果 透析液中乌头碱、次乌头碱和新乌头碱分别在 0.011 2 ～ 0.56 mg·L^-1 （ <> r =0.999 9 ） ， 0.010 6~0.53 mg·L^-1 （ <> r =0.999 7 ） 和 0.011 4 ～ 0.57 mg·L^-1 （ <> r =0.999 8 ） 内线性关系良好，方法回收率在 93.12% 以上。乌头碱、次乌头碱和新乌头碱的血药浓度 - 时间曲线均符合开放式二室模型。 结论 本实验建立的方法简便，专属灵敏， 可用于附子提取物中乌头类生物碱的药动学研究。

Simultaneous Pharmacokinetics of Three Aconitine-Type Alkaloids of Fuzi in Rats

OBJECTIVE To investigate pharmacokinetics of aconitine, hypaconitine and mesaconitine, three main effective components of Fuzi in rats using microdialysis sampling technique coupled with RP-HPLC method. METHODS After a single duodenum administration of Fuzi extract of 1 055 mg·kg-1 to SD rats, microdialysates from jugular vein were collected. Aconitine, hypaconitine and mesaconitine in dialysates were assayed by RP-HPLC simultaneously, and reverse microdialysis was used for recovery calibration to quantify the ‘‘true’’ concentration. The pharmacokinetic parameters were caculated by 3P97 pharmacokinetic program. RESULTS The linear range was 0.011 2-0.56 mg·L-1 (r=0.999 9), 0.010 6-0.53 mg·L-1 (r=0.999 7) and 0.011 4-0.57 mg·L-1(r=0.999 8) for aconitine, hypaconitine and mesaconitine in dialysate, respectively. The recovery of assay was above 93.12%. The concentration-time curves of aconitine, hypaconitine and mesaconitine were fitted to the two-compartment open model. CONCLUSION The method is simple, specific and sensitive, and suitable for pharmacokinetic study on aconitine-type alkaloids in the extract of Fuzi.