采用大体积直接进样 LC-MS/MS 法测定宝元汤 16 个代表性成分在大鼠血浆中的药代动力学。
Pharmacokinetics study of 16 representative components from Baoyuan Decoction in rat plasma by LC-MS/MS with a large-volume direct injection method.
机构信息
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
出版信息
Phytomedicine. 2019 Apr;57:148-157. doi: 10.1016/j.phymed.2018.09.002. Epub 2018 Sep 13.
BACKGROUND
Baoyuan decoction (BYD), a well-known traditional Chinese medicine (TCM) formula, is clinically used for the treatment of aplastic anemia, chronic renal failure, coronary heart disease, etc. PURPOSE: The purpose of this study was to develop a large-volume direct injection liquid chromatography-mass spectrometry (LC-MS) method for simultaneous determination of 16 representative flavonoids and saponins in rat plasma after oral administration of BYD.
METHODS
The rat plasma sample was injected directly into a pre-column, which was eluted firstly by 0.05% formic acid in water. Then, the accumulated components were eluted from the pre-column and transferred into a Waters BEH C18 column with acetonitrile and water system (contain 0.05% formic acid) as the mobile phase at a rate of 0.3 ml/min. The detection was accomplished in a negative mode using the schedule multiple-reaction monitoring (sMRM).
RESULTS
The correlation coefficients for calibration curves were all higher than 0.9920 for formononetin, ononin, calycosin, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, liquiritin, isoliquiritin, liquiritin apioside, isoliquiritin apioside, ginsenoside Rb1, ginsenoside Re, ginsenoside Rd, ginsenoside Rg1 and astragaloside. The intra- and inter-day precisions (RSD) and accuracy (RE) for the investigated components were in the range of -10.9 to 13.7%. The average recoveries were in the range of 75.7-108.6%. This method was successfully applied to investigate the pharmacokinetics of 16 compounds of BYD in rats. The absorption and elimination rates of the representative saponins were significantly slower than most of the targeted-flavonoids after oral administration of BYD in rats.
CONCLUSION
The results demonstrated that the large-volume direct injection LC-MS method provided a rapid and efficient approach for multi-components pharmacokinetics of TCM.
背景
宝元汤（BYD）是一种著名的中药（TCM）配方，临床上用于治疗再生障碍性贫血、慢性肾衰竭、冠心病等。目的：本研究旨在建立一种大体积直接进样液相色谱-质谱（LC-MS）法，用于同时测定大鼠口服 BYD 后血浆中 16 种代表性黄酮类和皂苷类成分。
方法
大鼠血浆样品直接注入预柱，首先用 0.05%甲酸水冲洗。然后，累积的成分从预柱洗脱并转移到 Waters BEH C18 柱中，以乙腈和水系统（含 0.05%甲酸）为流动相，以 0.3ml/min 的速度洗脱。检测采用负模式下的定时多反应监测（sMRM）进行。
结果
16 种化合物的校准曲线相关系数均大于 0.9920，其中包括芒柄花素、大豆苷元、大豆苷、甘草酸、甘草苷、甘草酸、甘草次酸、甘草苷、异甘草苷、甘草苷、异甘草苷、人参皂苷 Rb1、人参皂苷 Re、人参皂苷 Rd、人参皂苷 Rg1 和黄芪甲苷。所研究成分的日内和日间精密度（RSD）和准确度（RE）均在-10.9%至 13.7%范围内。平均回收率在 75.7%至 108.6%范围内。该方法成功应用于大鼠体内 BYD 16 种化合物的药代动力学研究。口服 BYD 后，代表性皂苷的吸收和消除速度明显比大多数靶向黄酮类化合物慢。
结论
结果表明，大体积直接进样 LC-MS 法为中药多成分药代动力学提供了一种快速有效的方法。
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