Simultaneous determination of four bioactive flavonoids from Polygonum orientale L. in dog plasma by UPLC-ESI-MS/MS and application of the technique to pharmacokinetic studies
Simultaneous determination of four bioactive flavonoids from Polygonum orientale L. in dog plasma by UPLC-ESI-MS/MS and application of the technique to pharmacokinetic studies
复制标题
UPLC-ESI-MS/MS同时测定狗血浆中东方蓼中4种生物活性黄酮类化合物及其在药代动力学研究中的应用
DOI：
10.1016/j.jchromb.2014.02.055
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发表时间：
2014-04-15
影响因子：
3
通讯作者：
Wu, Ji-zhou
中科院分区：
文献类型：
--
作者：
Huang, Yong;Zhang, Peng;Wu, Ji-zhou
传统草药的体内效应通常由多种生物活性成分介导。红蓼的主要化学成分是黄酮类化合物，如红蓼苷、牡荆苷、洋蓟苷和槲皮苷。本研究的目的是建立和验证一种用于鉴定这些黄酮类化合物的方法，以便更好地了解水青树的药代动力学和药效学。用甲醇沉淀蛋白质后，在BEH C-18柱（50 mm × 2.1 mm，同上，1.7μ m）。使用多反应监测（MRM）模式在m/z 449.2-> 329.2（对于Orientin）、m/z 433.2-> 313.0（对于Vitexin）、m/z 449.2-> 287.1（对于Cynaroside）、m/z 449.2-> 303.4（对于Quercitrin）和m/z 417.0-> 267.0（对于内标物葛根素）下测定黄酮含量。在比格犬中以22、44或88 mg/kg的剂量静脉内给予P. orientale L提取物（POE）后，评估了药代动力学。线性回归分析的标准曲线显示高线性超过243倍的动态范围内的四种黄酮类化合物（定量下限值为4 - 21 ng/mL）。日内和日间测定的相对标准偏差均小于15.1%，方法的准确度在-8.7%~7.2%之间，狗血浆中的提取回收率分别为70.6-89.3%、69.8-88.7%、72.5-85.7%和71.0-79.1%。分别我们的研究结果表明，非线性的药代动力学特征与快速清除类黄酮。结论：UPLC-ESI-MS/MS是一种快速、灵敏的同时测定犬血浆中POE中多种黄酮类化合物的方法，适用于中药的药代动力学研究。(C)2014爱思唯尔有限公司版权所有。
The in vivo effects of traditional herbal medicines are generally mediated by multiple bioactive components. The main constituents of Polygonum orientale L are flavonoids such as orientin, vitexin, cynaroside, and quercitrin. The aim of this study was to develop and validate a method for characterizing these flavonoids, in order to better understand the pharmacokinetics and pharmacodynamics of P. orientale L We used ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) to analyze the flavonoids. After precipitation of the proteins with methanol, the flavonoids were separated on a BEH C-18 column (50 mm x 2.1 mm, id., 1.7 mu m) by using an elution gradient of acetonitrile. Flavonoid content was determined using the multiple reaction monitoring (MRM) mode at m/z 449.2 -> 329.2 for orientin, m/z 433.2 -> 313.0 for vitexin, m/z 449.2 -> 287.1 for cynaroside, m/z 449.2 -> 303.4 for quercitrin, and m/z 417.0 -> 267.0 for the internal standard, puerarin. Pharmacokinetics was assessed after intravenous administration of P. orientale L extracts (POE) in Beagle dogs at a dose of 22, 44, or 88 mg/kg. Analysis of the standard curves by linear regression revealed high linearity over a 243-fold dynamic range for the four flavonoids (the lower limit of quantitation values were 4-21 ng/mL). The relative standard deviations of intra- and inter-day measurements were less than 15.1%, and the method was accurate to within -8.7% to 7.2%; the extraction recoveries from dog plasma were 70.6-89.3%, 69.8-88.7%, 72.5-85.7%, and 71.0-79.1% for orientin, vitexin, cynaroside, and quercitrin. respectively. Our results suggest non-linear pharmacokinetic characteristics with rapid clearance of the flavonoids. In conclusion, UPLC-ESI-MS/MS is a rapid and sensitive method for simultaneous quantification of multiple flavonoids from POE in dog plasma and is suitable for pharmacokinetic studies of herbal medicines. (C) 2014 Elsevier B.V. All rights reserved.