白芷香豆素类成分含量测定及药代动力学研究
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摘要
目的:建立HPLC方法测定白芷药材、提取物及制剂中的香豆素类成分的含量;建立LC/MS/MS分析方法,并对白芷中3个香豆素类成分大鼠体内的药代动力学及小鼠脑组织中分布的经时变化进行研究。
方法:利用HPLC方法测定白芷药材、提取物及制剂中香豆素类成分的含量。利用LC/MS/MS方测定血浆及脑组织中3个香豆素成分的浓度。采用脑组织匀浆法,测定小鼠灌胃给药后血浆及脑组织的分布。
结果:本实验建立的HPLC方法及LC/MS/MS分析方法具备良好的精密度、重复性和稳定性。小鼠给予白芷提取物后,3个香豆素类成分能够通过血脑屏障,并在脑组织中有较高分布。
结论:本实验建立的HPLC方法及LC/MS/MS方法准确灵敏,可用于香豆素类活性成分的含量测定及药代动力学研究。欧前胡素、8-氧甲基异欧前胡内酯、异欧前胡素的体内消除迅速且药代动力学个体差异比较大。3个成分能够通过血脑屏障,并在脑组织中有较高分布。
Objective: 1. To establish an HPLC method for the quantification of xanthotoxol, bergapten, imperatorin and isoimperatorin in Radix Angelicae dahuricae by HPLC; To establish a liquid chromatography electrospray ionisation–tandem mass spectrometry (LC/MS/MS) method used for the investigation of the pharmacokinetics of 3 coumarin components ( imperatorin, cnidilin and isoimperatorin); and investigate the distribution of the coumarin components in mice brain.
Methods: An HPLC method was used to simultaneous quantification of coumarin components in Radix Angelicae dahuricae extract. and Duliang capsules; A liquid chromatography–tandem mass spectrometry (LC/MS/MS) method was used for simultaneous determination of imperatorin, isoimperatorin and cnidilin in rat plasma. With the homogenation of brain tissue, the LC/MS/MS method was used to investigate the concentration of brain tissue and blood with respect to time as to reflect the distribution of the coumarin components in mice brain and the blood.
Results: An HPLC method has been established for simultaneous quantification of coumarin components in Radix Angelicae dahuricae extract and the precision, reproducibility, The LC/MS/MS method used for the analysis of biology samples and pharmacokinetic studies of coumarin components: The method was then applied in pharmacokinetic studies of imperatorin, isoimperatorin and cnidilin in rats after oral administration of Radix Angelicae dahuricae extract. It showed that imperatorin, cnidilin and isoimperatorinin could permeate the rat blood brain barrier and show a higher distribution in brain tissue after oral administration of Radix Angelicae dahuricae extract.
Conclusion: The HPLC method established in our lab proves to be simple and feasible which could be used to quantification of the courmain components in Radix Angelicae dahuricae and its formulations. The LC/MS/MS has been established to simultaneous quantification of imperatorin, cnidilin and isoimperatorin in rat plasma and its application in the pharmacokinetic studies of the 3 active courmain components after oral administration of Radix Angelicae dahuricae extract in rats. This method proved to be sensitive and specific, and precision. Imperatorin, cnidilin and isoimperatorinin could permeate the rat blood brain barrier and show a higher distribution in brain tissue after oral administration of Radix Angelicae dahuricae extract.
方法:利用HPLC方法测定白芷药材、提取物及制剂中香豆素类成分的含量。利用LC/MS/MS方测定血浆及脑组织中3个香豆素成分的浓度。采用脑组织匀浆法,测定小鼠灌胃给药后血浆及脑组织的分布。
结果:本实验建立的HPLC方法及LC/MS/MS分析方法具备良好的精密度、重复性和稳定性。小鼠给予白芷提取物后,3个香豆素类成分能够通过血脑屏障,并在脑组织中有较高分布。
结论:本实验建立的HPLC方法及LC/MS/MS方法准确灵敏,可用于香豆素类活性成分的含量测定及药代动力学研究。欧前胡素、8-氧甲基异欧前胡内酯、异欧前胡素的体内消除迅速且药代动力学个体差异比较大。3个成分能够通过血脑屏障,并在脑组织中有较高分布。
Objective: 1. To establish an HPLC method for the quantification of xanthotoxol, bergapten, imperatorin and isoimperatorin in Radix Angelicae dahuricae by HPLC; To establish a liquid chromatography electrospray ionisation–tandem mass spectrometry (LC/MS/MS) method used for the investigation of the pharmacokinetics of 3 coumarin components ( imperatorin, cnidilin and isoimperatorin); and investigate the distribution of the coumarin components in mice brain.
Methods: An HPLC method was used to simultaneous quantification of coumarin components in Radix Angelicae dahuricae extract. and Duliang capsules; A liquid chromatography–tandem mass spectrometry (LC/MS/MS) method was used for simultaneous determination of imperatorin, isoimperatorin and cnidilin in rat plasma. With the homogenation of brain tissue, the LC/MS/MS method was used to investigate the concentration of brain tissue and blood with respect to time as to reflect the distribution of the coumarin components in mice brain and the blood.
Results: An HPLC method has been established for simultaneous quantification of coumarin components in Radix Angelicae dahuricae extract and the precision, reproducibility, The LC/MS/MS method used for the analysis of biology samples and pharmacokinetic studies of coumarin components: The method was then applied in pharmacokinetic studies of imperatorin, isoimperatorin and cnidilin in rats after oral administration of Radix Angelicae dahuricae extract. It showed that imperatorin, cnidilin and isoimperatorinin could permeate the rat blood brain barrier and show a higher distribution in brain tissue after oral administration of Radix Angelicae dahuricae extract.
Conclusion: The HPLC method established in our lab proves to be simple and feasible which could be used to quantification of the courmain components in Radix Angelicae dahuricae and its formulations. The LC/MS/MS has been established to simultaneous quantification of imperatorin, cnidilin and isoimperatorin in rat plasma and its application in the pharmacokinetic studies of the 3 active courmain components after oral administration of Radix Angelicae dahuricae extract in rats. This method proved to be sensitive and specific, and precision. Imperatorin, cnidilin and isoimperatorinin could permeate the rat blood brain barrier and show a higher distribution in brain tissue after oral administration of Radix Angelicae dahuricae extract.
引文
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