目的：建立大鼠血浆中次乌头碱的LC-MS/MS 检测方法，用于研究附子配伍甘草后次乌头碱在大鼠体内药动学的变化。方法：大鼠分别灌服附子单煎液、附子甘草合煎液，其中次乌头碱含量分别为73.29 滋g·kg-1、34.85 滋g·kg-1，LC-MS/MS 测定次乌头碱血药浓度，采用3P97 药动学软件分别计算其药动学参数。结果：血浆中次乌头碱在1.98耀198 ng·mL-1 范围内呈现良好的线性关系。附子配伍甘草后次乌头碱在大鼠体内Tmax 显著延长，CL 显著减小，AUC/dosage 显著增大（P<0.05）。结论：附子配伍甘草后次乌头碱在大鼠体内药动学行为发生显著改变。

The study was aimed to establish a LC-MS/MS assay in the determination of hypaconitine in rat plasma.Pharmacokinetic changes of hypaconitine in rats for the compatibility of Radix Aconiti Lateralis with Radix Glycyrrhizae were also investigated. Rats were orally administrated with decoction of Radix Aconiti Lateralis and decoction of Radix Aconiti Lateralis and Radix Glycyrrhizae, respectively. And the contents of hypaconitine were 73.29μg/kg and 34.85 μg/kg, respectively. The contents of hypaconitine in rat plasma were detected by LC-MS/MS method. Pharmacokinetic parameters were calculated by 3P97 pharmacokinetic program. The results showed that the linear range of hypaconitine in plasma was 1.98-198 ng/mL. The pharmacokinetic parameters obtained showed that Cmax and AUC/dosage of hypaconitine were prolonged, while CL was decreased when Radix Aconiti Lateralis was combined with Radix Glycyrrhizae (P < 0.05). It was concluded that there were obvious effects on pharmacokinetic of hypaconitine in rats when Radix Aconiti Lateralis is combined with Radix Glycyrrhizae.

国家自然科学基金面上项目（81073070）：基于胃肠道吸收环节研究“四逆汤”附子畏甘草解毒作用机理；负责人：傅超美。