目的 建立HPLC-MS/MS法同時(shí)檢測大鼠ig大黃蒽醌后血漿中大黃酸、大黃素、蘆薈大黃素、大黃酚、大黃素甲醚和番瀉苷A，研究大黃蒽醌在大鼠體內(nèi)的藥動學(xué)。方法 采用Shim-pack VP-ODS C₁₈色譜柱（150 mm×2 mm，5 μm）；流動相為含0.1%甲酸、2 mmol/L乙酸銨的水溶液-乙腈，采用梯度洗脫方式；柱溫40℃；體積流量0.3 mL/min。采用電噴霧離子源（ESI），多重反應(yīng)監(jiān)測（MRM）模式掃描，負(fù)離子方式檢測。SD大鼠分別ig 37.5、75、150 mg/kg大黃蒽醌，分別于給藥后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法測定血藥濃度，繪制血藥濃度-時(shí)間曲線，采用WinNonlin軟件進(jìn)行數(shù)據(jù)分析，計(jì)算藥動學(xué)參數(shù)。結(jié)果 各蒽醌類成分在選定的質(zhì)量濃度范圍內(nèi)線性關(guān)系良好。在低、中、高3個質(zhì)量濃度下6種成分的提取回收率為88.22%~102.04%，基質(zhì)效應(yīng)為89.26%~106.01%。在37.5 mg/kg劑量組中，僅檢測到大黃酸、大黃素和蘆薈大黃素；在75、150 mg/kg劑量組中，檢測到大黃酸、大黃素、蘆薈大黃素和大黃酚。在3個劑量組中均未檢測到大黃素甲醚和番瀉苷A。大黃酸在體內(nèi)迅速吸收，3個劑量組中均在30 min內(nèi)就達(dá)到最大血藥濃度（C_max）。大黃酸、大黃素、蘆薈大黃素和大黃酚C_max和曲線下面積（AUC_0→∞）均隨劑量的增加而增加，具有劑量相關(guān)性。血漿清除率（CL/F）和表觀分布容積（V/F）不隨劑量增加而明顯改變，此4個成分藥動學(xué)標(biāo)志物的藥動學(xué)行為呈線性動力學(xué)特征。結(jié)論 建立了同時(shí)測定大鼠血漿中大黃酸、大黃素、蘆薈大黃素、大黃酚、大黃素甲醚和番瀉苷A 6種成分的HPLC-MS/MS方法，適用于大黃蒽醌在大鼠體內(nèi)的藥動學(xué)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.