目的:探讨彝药黑根治疗类风湿性关节炎潜在的作用机制以及主要活性成分。方法:运用UPLC-Q-Orbitrap HRMS及GC-MS技术分析黑根的化学成分,利用Swiss Target进行活性成分的靶点筛选和预测,同时在Genecard、OMIM、Dis Ge NET等数据库中筛...目的:探讨彝药黑根治疗类风湿性关节炎潜在的作用机制以及主要活性成分。方法:运用UPLC-Q-Orbitrap HRMS及GC-MS技术分析黑根的化学成分,利用Swiss Target进行活性成分的靶点筛选和预测,同时在Genecard、OMIM、Dis Ge NET等数据库中筛选类风湿性关节炎相关靶点,利用Cytoscape3.9.0软件构建“活性成分-靶点”网络模型,运用String数据分析平台进行蛋白互作网络分析,并且利用基因富集分析在线工具对核心靶点进行GO富集分析和KEGG通路分析,最后使用分子对接对网络药理学内容进行初步验证。结果:共鉴定出黑根化学成分78个,筛选后活性成分50个,237个潜在作用靶点与类风湿性关节炎相关,包括STAT3、AKT1、EGFR等关键靶点。通路富集分析PI3K-Akt通路、JAK-STAT等信号通路可能是黑根发挥抗类风湿性关节炎的主要途径。通过分子对接技术得出主要活性成分(异绿原酸B、异绿原酸C)与关键靶点有较好结合力。结论:研究初步表明黑根通过多成分、多靶点、多途径治疗类风湿性关节炎的作用,为后续黑根物质基础研究提供了理论依据。展开更多
Potential mutagenic impurities in Active Pharmaceutical Ingredient, Meropenem Trihydrate were assessed and a novel analytical method for their quantification was developed and validated. This Liquid Chromatographic me...Potential mutagenic impurities in Active Pharmaceutical Ingredient, Meropenem Trihydrate were assessed and a novel analytical method for their quantification was developed and validated. This Liquid Chromatographic method using High Resolution Mass Spectrometer (LC-HRMS) technique is proved to be suitable for simultaneous quantification of all ten identified impurities with required specificity, sensitivity, resolution, precision, accuracy, and other method characteristics as per ICH Guidelines. The acceptable limit of less than 2.9 μg/g was considered for evaluations, based on drug substance dosage and duration of treatment. The method stands most sensitive with a Limit of Detection of 0.35 μg/g, considering the challenge full acceptance criteria as per current regulatory standards.展开更多
目的建立虎地肠溶胶囊多成分定量方法,并结合化学计量学方法对其进行质量评价。方法采用超高效液相色谱—四极杆静电场轨道阱高分辨质谱法(ultra-performance liquid chromatography-quadrupole-electrostatic field Orbitrap high-reso...目的建立虎地肠溶胶囊多成分定量方法,并结合化学计量学方法对其进行质量评价。方法采用超高效液相色谱—四极杆静电场轨道阱高分辨质谱法(ultra-performance liquid chromatography-quadrupole-electrostatic field Orbitrap high-resolution mass spectrometry,UPLC-Orbitrap-HRMS)测定10批虎地肠溶胶囊中没食子酸、虎杖苷、甘草酸、白藜芦醇、鞣花酸、甘草素、甘草苷、大黄素、绿原酸、异甘草素、咖啡酸、木犀草素、芒柄花素、芹菜素、槲皮素和山柰酚的含量,并采用聚类分析、主成分分析、正交偏最小二乘法判别分析和灰色关联度分析对样品进行综合评价。结果16个成分线性关系良好,专属性、精密度、重复性、稳定性和平均加样回收率实验均符合标准。10批虎地肠溶胶囊被分为2类,甘草素、木犀草素、白藜芦醇、鞣花酸、槲皮素、山柰酚、咖啡酸、绿原酸和大黄素9个成分对样品质量的差异影响较大;以质量优劣情况对样品进行排序,第Ⅰ类样品的质量普遍劣于第Ⅱ类,木犀草素、鞣花酸、槲皮素、山柰酚、绿原酸和大黄素6个成分的含量偏低可能是第Ⅰ类样品质量低劣的原因。结论建立的虎地肠溶胶囊多成分定量方法结合化学计量学分析可用于该药物的质量评价。展开更多
文摘目的:探讨彝药黑根治疗类风湿性关节炎潜在的作用机制以及主要活性成分。方法:运用UPLC-Q-Orbitrap HRMS及GC-MS技术分析黑根的化学成分,利用Swiss Target进行活性成分的靶点筛选和预测,同时在Genecard、OMIM、Dis Ge NET等数据库中筛选类风湿性关节炎相关靶点,利用Cytoscape3.9.0软件构建“活性成分-靶点”网络模型,运用String数据分析平台进行蛋白互作网络分析,并且利用基因富集分析在线工具对核心靶点进行GO富集分析和KEGG通路分析,最后使用分子对接对网络药理学内容进行初步验证。结果:共鉴定出黑根化学成分78个,筛选后活性成分50个,237个潜在作用靶点与类风湿性关节炎相关,包括STAT3、AKT1、EGFR等关键靶点。通路富集分析PI3K-Akt通路、JAK-STAT等信号通路可能是黑根发挥抗类风湿性关节炎的主要途径。通过分子对接技术得出主要活性成分(异绿原酸B、异绿原酸C)与关键靶点有较好结合力。结论:研究初步表明黑根通过多成分、多靶点、多途径治疗类风湿性关节炎的作用,为后续黑根物质基础研究提供了理论依据。
文摘Potential mutagenic impurities in Active Pharmaceutical Ingredient, Meropenem Trihydrate were assessed and a novel analytical method for their quantification was developed and validated. This Liquid Chromatographic method using High Resolution Mass Spectrometer (LC-HRMS) technique is proved to be suitable for simultaneous quantification of all ten identified impurities with required specificity, sensitivity, resolution, precision, accuracy, and other method characteristics as per ICH Guidelines. The acceptable limit of less than 2.9 μg/g was considered for evaluations, based on drug substance dosage and duration of treatment. The method stands most sensitive with a Limit of Detection of 0.35 μg/g, considering the challenge full acceptance criteria as per current regulatory standards.
文摘目的建立虎地肠溶胶囊多成分定量方法,并结合化学计量学方法对其进行质量评价。方法采用超高效液相色谱—四极杆静电场轨道阱高分辨质谱法(ultra-performance liquid chromatography-quadrupole-electrostatic field Orbitrap high-resolution mass spectrometry,UPLC-Orbitrap-HRMS)测定10批虎地肠溶胶囊中没食子酸、虎杖苷、甘草酸、白藜芦醇、鞣花酸、甘草素、甘草苷、大黄素、绿原酸、异甘草素、咖啡酸、木犀草素、芒柄花素、芹菜素、槲皮素和山柰酚的含量,并采用聚类分析、主成分分析、正交偏最小二乘法判别分析和灰色关联度分析对样品进行综合评价。结果16个成分线性关系良好,专属性、精密度、重复性、稳定性和平均加样回收率实验均符合标准。10批虎地肠溶胶囊被分为2类,甘草素、木犀草素、白藜芦醇、鞣花酸、槲皮素、山柰酚、咖啡酸、绿原酸和大黄素9个成分对样品质量的差异影响较大;以质量优劣情况对样品进行排序,第Ⅰ类样品的质量普遍劣于第Ⅱ类,木犀草素、鞣花酸、槲皮素、山柰酚、绿原酸和大黄素6个成分的含量偏低可能是第Ⅰ类样品质量低劣的原因。结论建立的虎地肠溶胶囊多成分定量方法结合化学计量学分析可用于该药物的质量评价。
