银黄口服液血清药物化学的动态研究及其质量评价
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摘要
目的:建立简单、可靠的高效液相色谱法,用于银黄口服液血清药物化学的动态研究。并在此基础上,采用高效液相色谱-二极管阵列检测器-蒸发光散射联用技术,建立稳定可控的银黄制剂的双色谱指纹图谱,探讨主成分分析法和聚类分析法在银黄制剂双色谱指纹图谱中的应用。
方法:(1)采用Cosmosil-C18(5μm,4.6×150 mm),流动相采用1%醋酸(A)和乙腈(B)梯度洗脱法,建立银黄口服液以及大鼠口服银黄口服液后血清的HPLC指纹图谱,并在大鼠给药后不同时间采血以获得动态血清指纹图谱。
(2)采用HPLC-DAD-ELSD联用技术,建立了不同厂家的17个批次的银黄制剂的双色谱指纹图谱,并采用聚类分析和主成分分析法对该指纹图谱进行化学模式识别研究。
结果:(1)银黄口服液给药后血中出现了11个移行成分,7个为银黄口服液中含有的原型成分,4个可能为新产生的代谢产物或内源性物质。银黄口服液含量相对较大的5个原型成分在血清中未能检测出来,可能未被吸收,或者已经被转化成其他成分。初步确定血中移行成分的主要来源于金银花和黄芩,而绿原酸和黄芩苷既是入血的主要成分,又是众多代谢产物的前体化合物,因而其有可能是药效的主要物质基础。
(2)选用17批不同批次和厂家的银黄制剂样本,建立的银黄制剂指纹图谱表征了不同厂家和批次的制剂之间的客观差异,且聚类分析和主成分分析法均能对样品进行正确的分类,直观、准确地表达了样品的质量信息。
结论:(1)血中的移行成分以及代谢产物将成为银黄口服液的体内作用基础,其来源为银黄口服液中的主要物质,对其进行深入研究,将进一步阐明银黄口服液的作用机制和药效物质基础。
(2)银黄制剂的HPLC-DAD-ELSD双色谱指纹图谱反映的产品质量信息全面、科学,且相互弥补了单一色谱在质量评价中的局限性。聚类分析和主成分分析法能有效地应用于是银黄制剂的双色谱指纹图谱分析,为有效的控制该制剂的质量提供评价依据。
创新性:(1)首次建立了适合银黄口服液及其体内分析的HPLC方法,并将方法应用到银黄口服液的血清药物化学动态分析及药效物质基础研究中。
(2)首次建立了银黄制剂的HPLC-DAD-ELSD双色谱指纹图谱,并结合聚类分析和主成分分析法对其进行了模式识别研究。
Objective:An HPLC method was developed to investigate the dynamic fingerprints of serum pharmacochemistry of Yin-huang oral liquid.The HPLC-DAD-ELSD double-fingerprints were used to evaluate the quality of Yin-huang preparation effectively,and the hierarchical cluster analysis and principal component analysis were applied for the quality control of traditional Chinese medicine.
Methods:(1)Based on the established HPLC fingerprints of Yin-huang oral liquid,analysis and comparison were carried out among the HPLC profiles of rat serum samples obtained in different time after oral administration of Yin-huang oral liquid.The compounds absorbed into serum,the original crude drugs and their metabolites were identified.
(2)Fingerprints of 17 Yin-huang preparations samples from various manufacturers were obtained by HPLC-DAD-ELSD method.The technique of projection discriminate analysis based on hierarchical cluster analysis and principal component analysis was applied to investigate the experimental data.
Results:(1)Eleven compounds were detected gradually in rat plasma from 0～180 min after oral administration,seven of which are original form of the compounds in Yin-huang oral liquid and four are metabolites,and the content of them were different in different plasma samples.
(2)The fingerprints developed showed that there were differences among the Yin-huang preparation by different manufacturers.HPLC-DAD-ELSD fingerprints and the technique of projection discriminate analysis based on hierarchical cluster analysis and principal component analysis properly revealed the quality information apparently and accurately.
Conclusions:(1)The compounds absorbed into blood and its metabolites are the effective constituents and the original crude drugs are the main ingredient drugs of the preparation.The further investigation of serum pharmacochemistry can illuminate the mechanism and effect substances of Yin-huang oral liquid.
(2)This method using the hierarchical cluster analysis and principal component analysis can be effectively applied to control the quality of the traditional Chinese medicine.
New ideas:(1)The study on serum pharrnacochemistry of Yin-huang oral liquid in different times was investigated for the first time.
(2)The HPLC-DAD-ELSD double-fingerprints of Yin-huang preparations were developed for the first time,and the technique of projection discriminate analysis based on hierarchical cluster analysis and principal component analysis was used to quality assessment of Yin-huang preparations for the first time.
方法:(1)采用Cosmosil-C18(5μm,4.6×150 mm),流动相采用1%醋酸(A)和乙腈(B)梯度洗脱法,建立银黄口服液以及大鼠口服银黄口服液后血清的HPLC指纹图谱,并在大鼠给药后不同时间采血以获得动态血清指纹图谱。
(2)采用HPLC-DAD-ELSD联用技术,建立了不同厂家的17个批次的银黄制剂的双色谱指纹图谱,并采用聚类分析和主成分分析法对该指纹图谱进行化学模式识别研究。
结果:(1)银黄口服液给药后血中出现了11个移行成分,7个为银黄口服液中含有的原型成分,4个可能为新产生的代谢产物或内源性物质。银黄口服液含量相对较大的5个原型成分在血清中未能检测出来,可能未被吸收,或者已经被转化成其他成分。初步确定血中移行成分的主要来源于金银花和黄芩,而绿原酸和黄芩苷既是入血的主要成分,又是众多代谢产物的前体化合物,因而其有可能是药效的主要物质基础。
(2)选用17批不同批次和厂家的银黄制剂样本,建立的银黄制剂指纹图谱表征了不同厂家和批次的制剂之间的客观差异,且聚类分析和主成分分析法均能对样品进行正确的分类,直观、准确地表达了样品的质量信息。
结论:(1)血中的移行成分以及代谢产物将成为银黄口服液的体内作用基础,其来源为银黄口服液中的主要物质,对其进行深入研究,将进一步阐明银黄口服液的作用机制和药效物质基础。
(2)银黄制剂的HPLC-DAD-ELSD双色谱指纹图谱反映的产品质量信息全面、科学,且相互弥补了单一色谱在质量评价中的局限性。聚类分析和主成分分析法能有效地应用于是银黄制剂的双色谱指纹图谱分析,为有效的控制该制剂的质量提供评价依据。
创新性:(1)首次建立了适合银黄口服液及其体内分析的HPLC方法,并将方法应用到银黄口服液的血清药物化学动态分析及药效物质基础研究中。
(2)首次建立了银黄制剂的HPLC-DAD-ELSD双色谱指纹图谱,并结合聚类分析和主成分分析法对其进行了模式识别研究。
Objective:An HPLC method was developed to investigate the dynamic fingerprints of serum pharmacochemistry of Yin-huang oral liquid.The HPLC-DAD-ELSD double-fingerprints were used to evaluate the quality of Yin-huang preparation effectively,and the hierarchical cluster analysis and principal component analysis were applied for the quality control of traditional Chinese medicine.
Methods:(1)Based on the established HPLC fingerprints of Yin-huang oral liquid,analysis and comparison were carried out among the HPLC profiles of rat serum samples obtained in different time after oral administration of Yin-huang oral liquid.The compounds absorbed into serum,the original crude drugs and their metabolites were identified.
(2)Fingerprints of 17 Yin-huang preparations samples from various manufacturers were obtained by HPLC-DAD-ELSD method.The technique of projection discriminate analysis based on hierarchical cluster analysis and principal component analysis was applied to investigate the experimental data.
Results:(1)Eleven compounds were detected gradually in rat plasma from 0～180 min after oral administration,seven of which are original form of the compounds in Yin-huang oral liquid and four are metabolites,and the content of them were different in different plasma samples.
(2)The fingerprints developed showed that there were differences among the Yin-huang preparation by different manufacturers.HPLC-DAD-ELSD fingerprints and the technique of projection discriminate analysis based on hierarchical cluster analysis and principal component analysis properly revealed the quality information apparently and accurately.
Conclusions:(1)The compounds absorbed into blood and its metabolites are the effective constituents and the original crude drugs are the main ingredient drugs of the preparation.The further investigation of serum pharmacochemistry can illuminate the mechanism and effect substances of Yin-huang oral liquid.
(2)This method using the hierarchical cluster analysis and principal component analysis can be effectively applied to control the quality of the traditional Chinese medicine.
New ideas:(1)The study on serum pharrnacochemistry of Yin-huang oral liquid in different times was investigated for the first time.
(2)The HPLC-DAD-ELSD double-fingerprints of Yin-huang preparations were developed for the first time,and the technique of projection discriminate analysis based on hierarchical cluster analysis and principal component analysis was used to quality assessment of Yin-huang preparations for the first time.
引文
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