Jiang Li, Gao Meng, Qu Fei, Li Hui-lan, Yu Lan-bin, Rao Yi, Wang Yue-sheng, Xu Guo-liang
Zhongguo Zhong Yao Za Zhi. 2015 Jul;40(13):2649-55.
To establish a LC-MS/MS method to determine the concentrations of liquiritin, glycyrrhizin, glycyrrhetinic acid, amygdalin, amygdalin prunasin, ephedrine, pseudoephedrine and methylephedrine of Maxing Shigan decoction in rat plasma, and study the differences on their pharmacokinetic process in normal rats and RSV pneumonia model rats. After normal rats and RSV pneumonia model rats were orally administered with Maxing Shigan decoction, the blood was collected from retinal vein plexus of different time points. Specifically, tetrahydropalmatine was taken as internal standard for determining ephedrine, while chloramphenicol was taken as internal standard for determining other components. After plasma samples were pre-treated as the above, the supernatant was dried with nitrogen blowing concentrator and then redissolved with methylalcohol. The chromatography was eluted with mobile phase consisted of acetonitrile and 0.1% formic acid solution in a gradient manner. ESI sources were adopted to scan ingredients in ephedra in a positive ion scanning mode and other ingredientsin a negative ion scanning mode. The multiple-reaction monitoring (MRM) method was developed the plasma concentration of each active component. The pharmacokinetic parameters of each group were calculated by using Win-Nonlin 4.1 software and put into the statistical analysis. The result showed the plasma concentration of the eight active ingredients, i.e., liquiritin, glycyrrhizin, glycyrrhetinic acid, amygdalin, amygdalin prunasin, ephedrine, pseudoephedrine and methylephedrine within the ranges of 1.04-1040, 1.04-1040, 0.89-445, 1.05-4200, 1.25-2490, 0.3-480, 0.3-480, 0.3-480 microg x L(-1), with a good linearity and satisfactory precision, recovery and stability in the above ingredients. After modeling, except for glycyrrhetinic acid whose pharmacokinetic parameters were lacked due to the data missing, all of the rest components showed significant higher Cmax, AUC(0-1) and lower clearance rate (CL) than that of the normal group, indicating the increase in absorption in rats in the pathological state by reducing the clearance rate. The method is accurate and sensitive and so can be used to determine the plasma concentrations of the eight active ingredients in Maxing Shigan decoction. RSV pneumonia-infected rats absorbed more ingredients in Maxing Shigan decoction.
建立一种液相色谱-串联质谱（LC-MS/MS）法，用于测定大鼠血浆中麻杏石甘汤的甘草苷、甘草酸、甘草次酸、苦杏仁苷、苦杏仁酶解苷、麻黄碱、伪麻黄碱和甲基麻黄碱的浓度，并研究其在正常大鼠和呼吸道合胞病毒（RSV）肺炎模型大鼠体内药代动力学过程的差异。正常大鼠和RSV肺炎模型大鼠口服麻杏石甘汤后，于不同时间点从视网膜静脉丛采集血液。具体而言，以四氢巴马汀为内标测定麻黄碱，以氯霉素为内标测定其他成分。血浆样品按上述方法预处理后，上清液用氮气吹干浓缩器吹干，再用甲醇复溶。色谱采用乙腈和0.1%甲酸溶液组成的流动相进行梯度洗脱分离。采用电喷雾电离（ESI）源，以正离子扫描模式扫描麻黄中的成分，以负离子扫描模式扫描其他成分。采用多反应监测（MRM）法测定各活性成分的血浆浓度。用Win-Nonlin 4.1软件计算各组的药代动力学参数并进行统计分析。结果表明，甘草苷、甘草酸、甘草次酸、苦杏仁苷苦杏仁酶解苷、麻黄碱、伪麻黄碱和甲基麻黄碱这8种活性成分的血浆浓度在1.04 - 1040、1.04 - 1040、0.⑧9 - ④④⑤、1.0⑤ - ④②00、1.②⑤ - ②④⑨0、0.③ - ④⑧0、0.③ - ④⑧0、0.③ - ④⑧0 μg·L⁻¹范围内，具有良好的线性关系，且上述成分的精密度、回收率和稳定性均令人满意。造模后，除甘草次酸因数据缺失无法获得药代动力学参数外，其余各成分的Cmax、AUC(0 - 1)均显著高于正常组，清除率（CL）显著低于正常组，提示病理状态下大鼠通过降低清除率使吸收增加。该方法准确、灵敏，可用于测定麻杏石甘汤中8种活性成分的血浆浓度。RSV肺炎感染大鼠对麻杏石甘汤中成分的吸收增多。
