目的 建立快速、灵敏、简便的超高效液相色谱-串联质谱（UPLC-MS/MS）法同时测定大鼠血浆中芍药苷及其代谢产物芍药内酯苷的暴露量，并研究单次ig给予大鼠低、中、高剂量（20、60、120 mg/kg）的芍药苷水溶液后，芍药苷、芍药内酯苷在大鼠体内的药动学特征。方法 以栀子苷为内标，血浆样品经甲醇（含0.1%甲酸）沉淀蛋白后，通过ACQUITY UPLC BEH-C₁₈柱（50 mm×2.1 mm， 1.7 μm），以0.1%甲酸水溶液-乙腈为流动相梯度洗脱，色谱运行时间为4.5 min。采用电喷雾离子源（ESI），负离子扫描模式，以多反应监测方式（MRM）进行定量测定。结果 芍药苷、芍药内酯苷的标准曲线的线性范围均为2.00~400 ng/mL，定量下限均为2.00 ng/mL， 2者日内和日间精密度RSD均小于9.10%。芍药苷在低、中、高3个剂量给药组中的t_max分别为（1.56±0.62）、（1.13±0.35）、（1.28±1.92）h， C_max分别为（85.45±47.49）、（390.75±139.26）、（1 223.5±420.15） μg/L；其中芍药苷水溶液低、中剂量组未检测到代谢产物芍药内酯苷，芍药苷水溶液高剂量组芍药内酯苷的t_max为（1.81±0.53） h， C_max为（19.81±8.98） μg/L。结论 本方法简便、准确、专属性强，适用于芍药苷和芍药内酯苷在大鼠体内的药动学研究。

Objective A fast, sensitive and reliable method using UPLC-MS/MS system was established for simultaneous determination of paeoniflorin and its metabolite albiflorin in rat plasma. Paeoniflorin aqueous solution was orally given to rats at doses of 20, 60, and 120 mg/kg, respectively. The pharmacokinetic behaviors of paeoniflorin and albiflorin in rats were investigated. Methods Geniposide was used as internal standard, the plasma samples were pretreated using methanol to separate precipitated proteins. Aqueous solution (containing 0.1% formic acid)-acetonitrile was used as mobile phase, then Acquity UPLC BEH-C₁₈ (50 mm×2.1 mm, 1.7 μm) column was used with gradient elution in 4.5 min. Electrospray ionization in negative ion mode and multi-reaction monitoring (MRM) was used to determine the content. Results The linear range of paeoniflorin and albiflorin was 2.00-400 ng/mL, the lower limit of quantification was 2.00 ng/mL, and the intra-and inter-day precisions (RSD) were less than 9.10%. The parameters of paeoniflorin after single oral administration of three doses were as follows:t_max were (1.56 ±0.62), (1.13 ±0.35), and (1.28 ±1.92) h; C_max were (85.45 ±47.49), (390.75 ±139.26), and (1 223.5 ±420.15) μg/L. The parameters of albiflorin after single oral administration of the dose of 120 mg/kg were as follows:t_max was (1.81 ±0.53) h; C_max was (19.81 ±8.98) μg/L. Conclusion The method is simple, accurate and specific, and it is suitable for studying the pharmacokinetics of paeoniflorin and albiflorin in SD rats.

国家自然科学基金重点资助项目（81430095）；教育部博士点基金（20132134110006）；天津市应用基础及前沿技术研究计划（16JCYBJC27900）