Development of a UPLC-MS/MS bioanalytical method for the pharmacokinetic study of (-)-epiafzelechin, a flavan-3-ol with osteoprotective activity, in C57BL/6J mice
Development of a UPLC-MS/MS bioanalytical method for the pharmacokinetic study of (-)-epiafzelechin, a flavan-3-ol with osteoprotective activity, in C57BL/6J mice
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DOI：
10.1016/j.jchromb.2014.07.028
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发表时间：
2014-09-15
影响因子：
3
通讯作者：
Chan, Tak Hang
中科院分区：
文献类型：
--
作者：
Wong, Ka Chun;Law, Man Chun;Chan, Tak Hang
（-）-表阿夫泽莱欣是一种常见于植物来源的黄烷-3-醇。生物学研究表明，表阿夫泽莱欣可能具有抗炎、抗氧化和骨保护作用。然而，其在体内的有效性仍有待证实。建立了小鼠血浆中（-）-表阿夫泽莱欣的高效液相色谱-串联质谱（UPLC-MS/MS）检测方法。通过使用反相C18柱和由水（0.1%，v/v，甲酸）和0- 70%ACN（0.1%，v/v，甲酸）组成的16分钟梯度洗脱方案实现分离。发现（-）-表阿夫泽莱欣的定量下限为12.5 ng/mL。该方法线性关系良好（r（2）= 0.992）。日内和日间精密度在12%以内，准确度在97.6%~ 113.4%之间。通过静脉内（i. v.）和腹膜内（i. p.）注射，并在不同时间点收集血液。然后通过UPLC-MS/MS方法分析血浆，并构建静脉内和腹膜内注射（-）-表阿夫泽莱欣的血药浓度-时间曲线。静脉注射和腹腔注射后，（-）-表阿夫泽莱欣在血液中的最大浓度（C-max）分别为10.6和6.0 μ g/mL，而在腹腔注射中达到C-max的时间为15 min。静脉注射和腹腔注射后，（-）-表阿夫泽莱欣的分布半衰期分别为7.0和12.6 min。由于（-）-表阿夫泽莱欣在水中的高溶解度，发现（-）-表阿夫泽莱欣的静脉内和腹膜内注射中的一些PK参数相似。(C)2014爱思唯尔有限公司版权所有。
(-)-Epiafzelechin is a flavan-3-ol commonly found in plant source. Biological studies suggested that (-)epiafzelechin may have anti-inflammatory, anti-oxidant and bone-protective effect. However, it's in vivo efficacy remains to be demonstrated. A specific detection method for (-)-epiafzelechin was successfully developed by using UPLC-MS/MS to quantify the amount of (-)-epiafzelechin present in mice plasma after a liquid-liquid extraction by ethyl acetate. The separation was achieved by using a reversed-phase C18 column with a 16 min gradient elution protocol consisting of water (0.1%, v/v, formic acid) and 0-70% ACN (0.1%, v/v, formic acid). The lower limit of quantitation for (-)-epiafzelechin was found to be 12.5 ng/mL. This method exhibited a good linearity (r(2) = 0.992). The intra-day and inter-day precision were within 12%, while the accuracy was between 97.6 and 113.4%. A quantity of 10 mg/kg synthetic (-)epiafzelechin was administered to C57BL/6J mice by intravenous (i.v.) and intraperitoneal (i.p.) injections and the blood was collected at different time points. The plasma was then analyzed by the UPLC-MS/MS method, and the plasma drug concentration-time curves for i.v. and i.p. (-)-epiafzelechin injection were constructed. The maximum concentrations (C-max) of (-)-epiafzelechin in blood by i.v. and i.p. injection were found to be 10.6 and 6.0 mu g/mL, respectively, while the time for reaching C-max in i.p. injection was found to be 15 min. The distribution half-lives of (-)-epiafzelechin after i.v. and i.p. injection were found to be 7.0 and 12.6 min, respectively. Some of the PK parameters were found to be similar in both i.v. and i.p. injections of (-)-epiafzelechin owing to its high solubility in water. (C) 2014 Elsevier B.V. All rights reserved.