Tissue distribution model and pharmacokinetics of nuciferine based on UPLC-MS/MS and BP-ANN.
Tissue distribution model and pharmacokinetics of nuciferine based on UPLC-MS/MS and BP-ANN.
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发表时间：
2015-10
影响因子：
0.1
通讯作者：
Yanyan Xu;Shihui Bao;Weiqiang Tian;Congcong Wen;Lufeng Hu;Chongliang Lin
中科院分区：
文献类型：
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作者：
Yanyan Xu;Shihui Bao;Weiqiang Tian;Congcong Wen;Lufeng Hu;Chongliang Lin
荷叶碱具有显著的生物活性，被认为是一种很有前途的药物。本研究建立了一种灵敏、选择性强的超高效液相色谱-串联质谱（UPLC-MS/MS）方法，并验证了该方法用于组织和血浆中荷叶碱的测定。采用电喷雾离子源，以正离子模式操作;多反应监测（MRM）模式用于定量，使用目标碎片离子m/z 296.0→265.1（荷叶碱）和m/z 322.0→307.0（小檗红碱内标物（IS））。采用超高效液相色谱-串联质谱法研究荷叶碱在小鼠体内的组织分布和大鼠体内的药代动力学。结果表明，荷叶碱经肠道吸收后迅速分布于各组织。荷叶碱的生物利用度为17.9%。它可以通过血脑屏障，在肝脏和肾脏中的浓度最高，其次是脾、肺、心和脑。荷叶碱在组织和血浆中消除迅速，t1/2在5小时内。这些组织中的浓度彼此相关，并且可以通过反向传播人工神经网络模型进行预测。
Nuciferine has shown remarkable biological activities and been considered as a promising drug. In this study, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for determination of nuciferine in tissue and plasma. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 296.0→265.1 for nuciferine, and m/z 322.0→307.0 for berberrubine internal standard (IS). Based on the UPLC-MS/MS method, the tissue distribution profile of nuciferine in mice and plasma pharmacokinetics in rat were studied. The results showed nuciferine was absorbed through intestinal tract and distributed into tissues rapidly. The bioavailability of nuciferine was identified at 17.9%. It can across through blood brain barrier, the concentrations in liver and kidney are highest, then followed by spleen, lung heart and brain. Nuciferine is eliminated quickly in the tissues and plasma, the t1/2 within 5 hour. The concentrations in these tissues are correlated to each other, and can be predicted by a back-propagation artificial neural network model.