Pharmacokinetic, bioavailability, metabolism and plasma protein binding evaluation of NADPH-oxidase inhibitor apocynin using LC-MS/MS
Pharmacokinetic, bioavailability, metabolism and plasma protein binding evaluation of NADPH-oxidase inhibitor apocynin using LC-MS/MS
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DOI：
10.1016/j.jchromb.2015.01.025
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发表时间：
2015-03-15
影响因子：
3
通讯作者：
Bhatta, Rabi S.
中科院分区：
文献类型：
--
作者：
Chandasana, Hardik;Chhonker, Yashpal S.;Bhatta, Rabi S.
夹竹桃素是胡黄连的主要活性成分，通过抑制产生超氧化物的NADPH氧化酶而表现出强的抗炎活性。为了阐明详细的药代动力学特征，建立了大鼠和人血浆中夹竹桃麻素的高效液相色谱-串联质谱（LC-MS/MS）方法。据我们所知，这是第一个使用LC-MS/MS在生物基质中对夹竹桃麻素进行完整验证的方法。大鼠口服50 mg/kg夹竹桃麻素后迅速吸收，并在5 min内达到峰值血浆水平。此外，观察到血浆水平长达48 h。夹竹桃麻素的生物利用度为8.3%。在大鼠和人血浆中，体外血浆蛋白结合率分别为83.41-86.07%和71.39-73.34%。发现夹竹桃麻素在胃液（pH 1.2）、肠液（pH 6.8）和生理液（pH 7.4）中稳定，包括微粒体（大鼠和人）稳定性研究。此外，在任何这些研究中，夹竹桃麻素都没有转化成其二聚体形式二夹竹桃麻素。这里提供的数据提供了关于夹竹桃麻素的重要信息，以支持其药理学功效和作为潜在抗炎药物候选物的进一步开发。(C)2015年由Elsevier B. V.出版
Apocynin is a major active constituent of Picrorhiza kurroa that exhibits potent anti-inflammatory activity by inhibiting superoxide-generating NADPH oxidase enzyme. To elucidate detailed pharmacokinetic profile of apocynin, high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed in rat and human plasma. To the best of our knowledge, this is the first method for complete validation of apocynin in biological matrix using LC-MS/MS. Apocynin was rapidly absorbed after oral administration at 50 mg/kg in rats and peak plasma level achieved within 5 min. Moreover, plasma levels were observed up to 48 h. The bioavailibity of apocynin was found to be 8.3%. In vitro plasma protein binding was found to be 83.41-86.07% and 71.39-73.34% in rat and human plasma, respectively. Apocynin was found stable in gastric (pH 1.2), intestinal (pH 6.8) and physiological (pH 7.4) fluids including microsomal (rat and human) stability studies. Further, apocynin did not convert to its dimeric form diapocynin in any of these studies. The data presented here provide crucial information about apocynin to support its pharmacological efficacy and further development as a potential anti-inflammatory drug candidate. (C) 2015 Published by Elsevier B.V.