目的 建立HPLC-MS/MS法同时检测大鼠ig大黄蒽醌后血浆中大黄酸、大黄素、芦荟大黄素、大黄酚、大黄素甲醚和番泻苷A，研究大黄蒽醌在大鼠体内的药动学。方法 采用Shim-pack VP-ODS C₁₈色谱柱（150 mm×2 mm，5 μm）；流动相为含0.1%甲酸、2 mmol/L乙酸铵的水溶液-乙腈，采用梯度洗脱方式；柱温40℃；体积流量0.3 mL/min。采用电喷雾离子源（ESI），多重反应监测（MRM）模式扫描，负离子方式检测。SD大鼠分别ig 37.5、75、150 mg/kg大黄蒽醌，分别于给药后0、0.083、0.25、0.5、0.75、1、2、3、4、6、8、12、24 h取血，采用HPLC-MS/MS法测定血药浓度，绘制血药浓度-时间曲线，采用WinNonlin软件进行数据分析，计算药动学参数。结果 各蒽醌类成分在选定的质量浓度范围内线性关系良好。在低、中、高3个质量浓度下6种成分的提取回收率为88.22%~102.04%，基质效应为89.26%~106.01%。在37.5 mg/kg剂量组中，仅检测到大黄酸、大黄素和芦荟大黄素；在75、150 mg/kg剂量组中，检测到大黄酸、大黄素、芦荟大黄素和大黄酚。在3个剂量组中均未检测到大黄素甲醚和番泻苷A。大黄酸在体内迅速吸收，3个剂量组中均在30 min内就达到最大血药浓度（C_max）。大黄酸、大黄素、芦荟大黄素和大黄酚C_max和曲线下面积（AUC_0→∞）均随剂量的增加而增加，具有剂量相关性。血浆清除率（CL/F）和表观分布容积（V/F）不随剂量增加而明显改变，此4个成分药动学标志物的药动学行为呈线性动力学特征。结论 建立了同时测定大鼠血浆中大黄酸、大黄素、芦荟大黄素、大黄酚、大黄素甲醚和番泻苷A 6种成分的HPLC-MS/MS方法，适用于大黄蒽醌在大鼠体内的药动学研究。

Objective To establish HPLC-MS/MS method for the determination of rhein, emodin, aloe-emodin, chrysophanol, physcion and sennoside A from rhubarb anthraquinones in rats plasma, and study pharmacokinetics of hubarb anthraquinones in rat. Methods HPLC-MS/MS method was adopted on Shimadzu VP-ODS C₁₈ column (150 mm×2 mm, 5 μm). The mobile phase was consisted of water (0.1% formic acid and 2 mmol/L ammonium acetate)-acetonitrile with gradient elution at a flow rate of 0.3 mL/min, and the temperature was 40℃. Electrospray ionization (ESI) source and multiple-reaction monitoring (MRM) was performed in the negative ion mode. SD rats were ig administered with 37.5, 75, and 150 mg/kg rhubarb anthraquinone, respectively, an then serial blood samples were collected at 0, 0.083, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, and 24 h, respectively. The plasma concentration was determined by HPLC-MS/MS method, and Mean plasma concentration-time curves were drawn. The data were analyzed by WinNonlin software, and the pharmacokinetic parameters were calculated. Results There were good linear relationships of rhubarb anthraquinones in the concentration ranges. Under low, medium, and high concentrations, the extraction recovery and matrix effect were 88.22%-102.04% and 89.26%-106.01%, respectively. Rhein, emodin, and aloe emodin were detected only in 37.5 mg/kg dose group. Rhein, emodin, aloe emodin, and chrysophanol were detected in 75 and 150 mg/kg dose groups. Emodin and sennoside A were not detected in all three groups. Rhein was absorbed rapidly and the maximum blood concentration (C_max) was reached within 30 min in three dose groups. C_max and AUC_0→∞ of rhein, emodin, aloe emodin, and chrysophanol were increased with the increase of dose, and it had a dose-dependent manner. The plasma clearance rate (CL/F) and apparent distribution volume (V/F) did not change significantly with the increase of dose. The pharmacokinetic behavior of these 4 rhubarb anthraquinones showed a linear dynamic characteristic. Conclusion HPLC-MS/MS method is established for the simultaneous determination of rhein, emodin, aloe emodin, chrysophanol, emodin and sennoside A in rat plasma, which is suitable for pharmacokinetic study of rhubarb Anthraquinones in rats.