中国中药杂志

2018, v.43(01) 174-182

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丹参酮Ⅰ和丹参酮Ⅱ_A在大鼠体内的代谢物研究
Metabolites of tanshinone Ⅰ and tanshinone Ⅱ_A in vivo in rats

赵文靖;黄漠然;尚展鹏;王子健;王志斌;张加余;
ZHAO Wen-jing;HUANG Mo-ran;SHANG Zhan-peng;WANG Zi-jian;WANG Zhi-bin;ZHANG Jia-yu;School of Chinese Pharmacy,Beijing University of Chinese Medicine;Beijing Institution of Chinese Medicine,Beijing University of Chinese Medicine;

摘要(Abstract):

该文采用UHPLC-LTQ-Orbitrap高分辨质谱技术分析鉴定丹参酮Ⅰ和丹参酮ⅡA在大鼠体内的代谢产物。灌药后,收集大鼠血浆和尿液。经固相萃取法处理生物样品后,采用Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm,1.7μm)色谱柱和0.1%甲酸水溶液(A)-乙腈(B)流动相系统进行梯度洗脱;在正离子模式下对含药血浆、尿液及空白组样品进行分析。最终通过分析精确质量数据、多级质谱信息与文献报道结果比对,共从大鼠生物样品中初步检测鉴定出26个代谢产物。其中7个为丹参酮Ⅰ的代谢产物,主要代谢途径为葡萄糖醛酸化、羟基化、还原反应、去甲基化反应、甲基化、硫酸酯化以及它们的复合反应等;19个为丹参酮ⅡA的代谢产物,其主要代谢途径为羟基化、还原反应、甲基化、硫酸酯化、葡萄糖结合、葡萄糖醛酸化以及它们的复合反应。结果表明,应用UHPLC-LTQ-Orbitrap高分辨液质联用技术可以较为全面地阐明丹参酮Ⅰ和丹参酮ⅡA在大鼠体内的代谢情况,可为进一步的药效学和毒理学再研究以及药物二次研发提供物质基础。
An efficient method of ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap(UHPLCLTQ-Orbitrap) mass spectrometer was established to elucidate the in vivo metabolites of tanshinone I and tanshinone ⅡAin rats.Urine and plasma samples were collected after oral gavage.After processing biological sample by solid phase extraction,Waters ACQUITY HPLC BEH C_(18) column(2.1 mm×100 mm,1.7 μm) was used with 0.1% formic acid(A)-acetonitrile(B) solution as the mobile phase for gradient elution.The plasma,urine and the blank samples were then analyzed by ESI-LTQ-Orbitrap equipped with an ESI ion source under positive ion mode.On the basis of the accurate mass measurements,multiple mass spectra and comparison of data with published literature,a total of 26 metabolites were tentatively identified and characterized in the rat samples.Among them,7 metabolites were derived from tanshinone I through metabolic pathways of glucuronide conjugation,hydroxylation,reduction reaction,demethylation reaction,methylation,sulfate conjugation and their composite reactions.Nineteen metabolites were derived from tanshinone ⅡA through metabolic pathways of hydroxylation,reduction reaction,methylation,sulfate conjugation,glucuronidation,glucosylation and their complicated reactions.The results showed that the metabolism of tanshinone I and tanshinone ⅡAin rats could be comprehensively clarified by using UHPLC-LTQ-Orbitrap mass spectrometer,providing material basis for the further research in terms of pharmacodynamics,toxicology,and secondary development of Chinese medicine.

关键词(KeyWords): 丹参酮Ⅰ;丹参酮ⅡA;UHPLC-LTQ-Orbitrap;代谢产物
tanshinone Ⅰ;tanshinone ⅡA;UHPLC-LTQ-Orbitrap;metabolites

Abstract:

Keywords:

基金项目(Foundation): 2017年北京市科技新星与领军人才培养专项计划(Z171100001117029)

作者(Authors): 赵文靖;黄漠然;尚展鹏;王子健;王志斌;张加余;
ZHAO Wen-jing;HUANG Mo-ran;SHANG Zhan-peng;WANG Zi-jian;WANG Zhi-bin;ZHANG Jia-yu;School of Chinese Pharmacy,Beijing University of Chinese Medicine;Beijing Institution of Chinese Medicine,Beijing University of Chinese Medicine;

DOI: 10.19540/j.cnki.cjcmm.2018.0005

参考文献(References):

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