二萜生物碱的分离纯化及中药指纹图谱研究
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摘要
二萜生物碱是乌头属、翠雀属、飞燕草属及绣线菊属植物中的活性成分,具有镇痛、抗炎和抗心律失常等生理活性作用。从植物中提取分离二萜生物碱一直是科研工作者关注的课题。本文采用反相高效液相制备色谱分离纯化二萜生物碱,并分别采用HPLC-MS技术和1HNMR技术,建立了草乌等药材的质量控制方法。具体内容如下：
在反相高效液相色谱法中,生物碱的色谱峰拖尾是一种长期存在的现象,它将降低生物碱的分离分析效果。本文研究了色谱柱和流动相对二萜生物碱分离的影响,经筛选确定色谱柱为HCEC18,流动相为0.2%甲酸水溶液-乙腈,二萜生物碱的拖尾现象得以有效消除,首次在酸性流动相且不加盐的条件下,以反相高效液相制备色谱分离纯化二萜生物碱。以草乌中二萜生物碱为目标化合物,对新方法进行分离验证,取得较好的实验结果：从草乌粗产品中分离出4个二萜生物碱,其纯度均高于98.0%。通过NMR和MS对其进行了结构鉴定,确定2个已知二萜生物碱：乌头碱和14-苯甲酰乌头原碱,同时发现2个新二萜生物碱：1,15-dimethoxy-3-hydroxy-14-benzoyl-16-ketoneoline和8-ethoxyl-14-Benzoyl-15-methyoxyaconine。
当草乌中二萜生物碱和其它组分同时检测,非二萜生物碱很难一起被检测出,致使样品信息不完整。本文采用HPLC-MS技术,建立了草乌的指纹图谱。本方法能有效增加指纹图谱的信息量,更准确反映样品的特征。同时用中药指纹图谱相似度评价软件对不同来源的草乌及其炮制品进行可量化的分析,得到其相似度值,进而对样品进行有效的鉴定,绘制特征指纹曲线,通过聚类分析来直观显示样品的近似程度和差异。结果显示本指纹图谱具有一定的专属性,能够反映草乌及其炮制品质量的差异。
建立了一种基于大孔吸附树脂法的中药1HNMR指纹图谱方法。采用大孔吸附树脂富集草乌等药材中的有效成分,以1HNMR为检测手段,结合主成分分析和系统聚类分析,进一步评价样品的质量。本指纹图谱方法具有较高的重复性和特征性,能够准确反映中药中有效成分的分布。
Diterpenoid alkaloids are active ingredients in species, such as Aconitum, Delphinium, Larspur, and Spiraea, which have analgesic, anti-inflammatory and anti-arrhythmic effect. According to the probiems to be sovled in separation and quality control of diterpenoinds alkaloids, we established a new for method for producing alkaloids with preparative RP-HPLC. Furthermore, HPLC-MS and1H NMR were constructed for quality control of Aconitumsnezoffii Reichb. The main results are listed as follows:
In order to eliminate the effect of peak tailing in RP-HPLC, HCEC18under acid mobile phase without salt was constructed to separate diterpenoid alkaloids. Aconitine,14-Benzoylaconine, and two new compounds had been isolated for the first time from Aconitum kusnezoffii Reichb. The structures had been comfirmed by analyzing spectra of MS and NMR. Two new compounds were1,15-dimethoxy-3-hydroxy-14-benzoyl-16-ketoneoline and8-ethoxyl-14-benzoyl-15-methyoxyaconine.
A high performance liquid chromatography method coupled with mass spectrometry has been developed to simultaneously analyse diterpenoind alkaloids. Using relative retention time and relative peak area as parameters, the similariry evaluation system was used to appraise the silimarity. Furthermore, character curve and Hierarchical cluster analysis was plotted to show visual representation the similarity of different sample. This technique was applied to the fingerprint research of Aconitum kusnezoffii Reichb.
Combined with macroprous adsorption resin, Hydrogen nuclear magnetic resonance has been applied to the determinination of active ingredients in plants. According to chemical identification methods, such as the similariry evaluation system, Hierarchical cluster analysis and principal component analysis, the menthod can be used for quality control of herbs.
在反相高效液相色谱法中,生物碱的色谱峰拖尾是一种长期存在的现象,它将降低生物碱的分离分析效果。本文研究了色谱柱和流动相对二萜生物碱分离的影响,经筛选确定色谱柱为HCEC18,流动相为0.2%甲酸水溶液-乙腈,二萜生物碱的拖尾现象得以有效消除,首次在酸性流动相且不加盐的条件下,以反相高效液相制备色谱分离纯化二萜生物碱。以草乌中二萜生物碱为目标化合物,对新方法进行分离验证,取得较好的实验结果：从草乌粗产品中分离出4个二萜生物碱,其纯度均高于98.0%。通过NMR和MS对其进行了结构鉴定,确定2个已知二萜生物碱：乌头碱和14-苯甲酰乌头原碱,同时发现2个新二萜生物碱：1,15-dimethoxy-3-hydroxy-14-benzoyl-16-ketoneoline和8-ethoxyl-14-Benzoyl-15-methyoxyaconine。
当草乌中二萜生物碱和其它组分同时检测,非二萜生物碱很难一起被检测出,致使样品信息不完整。本文采用HPLC-MS技术,建立了草乌的指纹图谱。本方法能有效增加指纹图谱的信息量,更准确反映样品的特征。同时用中药指纹图谱相似度评价软件对不同来源的草乌及其炮制品进行可量化的分析,得到其相似度值,进而对样品进行有效的鉴定,绘制特征指纹曲线,通过聚类分析来直观显示样品的近似程度和差异。结果显示本指纹图谱具有一定的专属性,能够反映草乌及其炮制品质量的差异。
建立了一种基于大孔吸附树脂法的中药1HNMR指纹图谱方法。采用大孔吸附树脂富集草乌等药材中的有效成分,以1HNMR为检测手段,结合主成分分析和系统聚类分析,进一步评价样品的质量。本指纹图谱方法具有较高的重复性和特征性,能够准确反映中药中有效成分的分布。
Diterpenoid alkaloids are active ingredients in species, such as Aconitum, Delphinium, Larspur, and Spiraea, which have analgesic, anti-inflammatory and anti-arrhythmic effect. According to the probiems to be sovled in separation and quality control of diterpenoinds alkaloids, we established a new for method for producing alkaloids with preparative RP-HPLC. Furthermore, HPLC-MS and1H NMR were constructed for quality control of Aconitumsnezoffii Reichb. The main results are listed as follows:
In order to eliminate the effect of peak tailing in RP-HPLC, HCEC18under acid mobile phase without salt was constructed to separate diterpenoid alkaloids. Aconitine,14-Benzoylaconine, and two new compounds had been isolated for the first time from Aconitum kusnezoffii Reichb. The structures had been comfirmed by analyzing spectra of MS and NMR. Two new compounds were1,15-dimethoxy-3-hydroxy-14-benzoyl-16-ketoneoline and8-ethoxyl-14-benzoyl-15-methyoxyaconine.
A high performance liquid chromatography method coupled with mass spectrometry has been developed to simultaneously analyse diterpenoind alkaloids. Using relative retention time and relative peak area as parameters, the similariry evaluation system was used to appraise the silimarity. Furthermore, character curve and Hierarchical cluster analysis was plotted to show visual representation the similarity of different sample. This technique was applied to the fingerprint research of Aconitum kusnezoffii Reichb.
Combined with macroprous adsorption resin, Hydrogen nuclear magnetic resonance has been applied to the determinination of active ingredients in plants. According to chemical identification methods, such as the similariry evaluation system, Hierarchical cluster analysis and principal component analysis, the menthod can be used for quality control of herbs.
引文
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