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Development and validation of a reversed‐phase HPLC method for CYP1A2 phenotyping by use of a caffeine metabolite ratio in saliva
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Elias Begas Evangelos Kouvaras Andreas K. Tsakalof Maria Bounitsi Eftihia Konstadinos Asprodini 《Biomedical chromatography : BMC》2015,29(11):1657-1663
CYP1A2 is important for metabolizing various clinically used drugs. Phenotyping of CYP1A2 may prove helpful for drug individualization therapy. Several HPLC methods have been developed for quantification of caffeine metabolites in plasma and urine. Aim of the present study was to develop a valid and simple HPLC method for evaluating CYP1A2 activity during exposure in xenobiotics by the use of human saliva. Caffeine and paraxanthine were isolated from saliva by liquid‐liquid extraction (chlorophorm/isopropanol 85/15v/v). Extracts were analyzed by reversed‐phase HPLC on a C18 column with mobile phase 0.1% acetic acid/methanol/acetonitrile (80/20/2 v/v) and detected at 273nm. Caffeine and paraxanthine elution times were <13min with no interferences from impurities or caffeine metabolites. Detector response was linear (0.10–8.00µg/ml, R2>0.99), recovery was >93% and bias <4.47%. Intra‐ and inter‐day precision was <5.14% (n=6). The limit of quantitation was 0.10µg/ml and the limit of detection was 0.018±0.002µg/mL for paraxanthine and 0.032±0.002µg/ml for caffeine. Paraxanthine/caffeine ratio of 34 healthy volunteers was significantly higher in smokers (p<0.001). Saliva paraxanthine/caffeine ratios and urine metabolite ratios were highly correlated (r=0.85, p<0.001). The method can be used for the monitoring of CYP1A2 activity in clinical practice and in studies relevant to exposure to environmental and pharmacological xenobiotics. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
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驱虫斑鸠菊化学成分的研究 总被引:7,自引:0,他引:7
从驱虫斑鸠菊(Vernonia anthelmintica Willd)的种子中分离到十个化合物, 经理化性质及波谱分析鉴定为斑鸠菊黄烷苷-对羟苯甲酯(p-Hydroxy benzoyl-Vemovan)(1)、斑鸠菊黄烷苷(Vernovan)(2), 为未见文献报道新化合物, 并发现斑鸠菊大苦素(Vernadalin)(3)、斑鸠菊醇(Vernodalol)(4), 对P388白血病细胞有抑制作用,5,6,7,8及10为该属植物中首次获得。 相似文献
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五味子酯J和五内酯F的分离与结构 总被引:5,自引:0,他引:5
从长梗南五味子(Kadsura Lorgipedunculata Finet.et Gagnep)种子中分得2个新化合物: 五味子酯(schisantherin)J(1)和五内酯(schisanlactone)F(2); 4个已知物: 五内酯(Schisanlactone)A、schizandronic acid、表安五酸(epianwuweizic acid)和二甲基去当归酰五味子酯F, 抗癌药理筛选表明, 在体外2对白血病P-388细胞有明显抑制作用。 相似文献
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中药有效成分三维结构数据库的开发和研究 总被引:11,自引:0,他引:11
介绍了北京大学中药有效成分三维结构数据库软件系统的结构、功能及开发步骤。该数据库系统不仅仅提供6500个中草药有效成分的二维和三维结构以及其它各类相关信息,同时拥有功能强大的数据库查询、维护及分子表达系统。在该系统中,用户可以交互式地实现多种分子特征的查询以及二维子结构的查询。查询得到的分子可以直接在北京大学药物设计系统(PKUDDS)中进行三维结构的显示和分析。该数据库系统和我们科研组开发的北京大学药物设计系统以及中草药信息系统构成了完整的基于中药的药物设计系统。该系统已经用于NS3-NS4A蛋白酶抑制剂以及其它体系的研究并取得了很好的结果。 相似文献
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本文首次报道了异黑豆素类似物, 6-非环糖基-4',7一二羟基黄酮的合成, 以2,4-二羟基苯甲酸为原料, 溴化和脱羧后以苄基作为羟基保护基, 通过Grignarcl反应获得具有各种不同侧链的中间体7,7氢解脱除苄基再用Fries重排或Frieclel-Crafts反应得到了C-Z酰化产物, 接着用碱缩合生成查尔酮, 经I2/H2SO4/DM SO氧化环合得到目标产物。 相似文献
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烯酮类化合物发光行为的研究 总被引:1,自引:0,他引:1
本工作合成了几种带桥键结构的烯酮类化合物, 研究了它们的光谱和光物理行为.结果表明那些分子内的双键因桥键化而成环的化合物具有很强的荧光量子产率,相反那些未桥键化或桥键化而双键未处于环内者则仅有较弱的荧光强度, 工作中还观察到该类化合物的"负溶致动力学效应"以及其荧光强度强烈地依赖于所用溶剂极性等现象,对所得结果进行了初步的讨论. 相似文献
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3’-大豆甙元磺酸钠的电化学行为及应用研究 总被引:27,自引:2,他引:27
采用线性扫描伏安法、循环伏安法和常规脉冲伏安法电化学手段详细研究了改 性药物3’-大豆甙元磺酸钠(3’-daidzein sulfonic sodium,Dss)在pHl.0—6. 2的水溶液中的电化学行为.在不同pH范围内得到了Das的三个还原波.研究证实, 在pH<3.2条件下所获得的Pcl,Pc2波分别为质子化的Dss的单电子不可逆吸附还 原波及还原中间体自由基的单电子单质子不可逆吸附还原波;在3.2<pH<6.2条 件下所获得的Pc3波,属于Dss后随质子化的单电子不可逆吸附还原波,而还原中间 体自由基的单电子波被氢波掩盖.测得在单分子层饱和吸附的条件下,每一个Dss 分子所占汞电极面积为0.664nm^2.此外,通过邻苯三酚自氧化产生活性氧自由基再 还原,对Dss清除活性氧自由基能力进行了研究,从电化学角度对其药理机制进行 了探讨,研究证实Dss具有较强的抗氧化性,是一种有效的活性氧自由基清除剂. 相似文献
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《Composite Interfaces》2013,20(7-9):661-670
Poly(N-isopropylacrylamide) (PNIPA) gel containing polymer surfactant poly(2-(methacryloyloxyl)decylphosphate) (PMDP) was synthesized and was found to show rapid volume phase transition above its transition temperature. Interestingly, the phase transition temperature of the PNIPA–PMDP gel was equal to that of the PNIPA gels alone. The concentration gradient of PMDP within the PNIPA gel can be obtained by applying an electric field on the gel, similar to the gel electrophoretic technique. The PMDP-gradient PNIPA gel clearly demonstrated the prevention of skin formation and the acceleration of the phase transition rate of the PNIPA gel by PMDP. The rapid volume phase transition allows potential applications of the PNPA–PMDP gel to soft actuators and drug delivery systems. Recently we also succeeded in synthesizing cylindrical microgels (0.8 μm in diameter, 5 μm in length) by a novel strategy where template-guiding synthesis and photochemical polymerization are combined. The obtained microgels can be characterized in individual level by a laser-trapping/Raman spectroscopy. In this article we also briefly described a famous gel system containing ionic surfactant capable of electrically driven actuators although it is not PNIPA gel. 相似文献