药学学报, 2021, 56(3): 841-848
引用本文:
伍鹏程, 赵盼, 罗兴平, 王云洁, 魏小宁, 郝泉, 刘鹏伟, 蔺瑞丽, 倪琳, 宋平顺, 柳军玺. 化学转化法间接测定当归药材中药效标志物藁本内酯含量的方法研究及应用[J]. 药学学报, 2021, 56(3): 841-848.
WU Peng-cheng, ZHAO Pan, LUO Xing-ping, WANG Yun-jie, WEI Xiao-ning, HAO Quan, LIU Peng-wei, LIN Rui-li, NI Lin, SONG Ping-shun, LIU Jun-xi. Development and application of a chemical transformational method for the indirect measurement of ligustilide content in Angelica sinensis[J]. Acta Pharmaceutica Sinica, 2021, 56(3): 841-848.

化学转化法间接测定当归药材中药效标志物藁本内酯含量的方法研究及应用
伍鹏程1,2, 赵盼1, 罗兴平3, 王云洁4, 魏小宁1, 郝泉4, 刘鹏伟5, 蔺瑞丽6, 倪琳6, 宋平顺6, 柳军玺1
1. 中国科学院兰州化学物理研究所, 中国科学院西北特色植物资源化学重点实验室, 甘肃省天然药物重点实验室, 甘肃 兰州 730000;
2. 中国科学院大学, 北京 100049;
3. 西北民族大学化学化工学院, 甘肃 兰州 730030;
4. 兰州佛慈制药股份有限公司, 甘肃 兰州 730046;
5. 甘肃岷县当归研究院, 甘肃 定西 748400;
6. 甘肃省药品检验研究院, 甘肃 兰州 730000
摘要:
藁本内酯化学结构决定其稳定性较差,无合格的藁本内酯对照品供应,无法满足含量控制的需求,本文通过关键转化反应条件的优化、HPLC-DAD方法学研究建立了间接测定当归药材中藁本内酯含量的方法,并分析大样本的含量测定数据为国家药典标准提出建议。研究确定机械搅拌下通过甲醇/环丙胺混合反应、提取溶剂对药材粉末的提取、反应同步处理以及超声辅助提取、反应处理过程可以达到稳定和转化藁本内酯的双重效果;通过外标法准确测定转化液中的环丙藁本含量进而间接计算当归药材中的藁本内酯的含量。对68份药材原产地样本(甘肃、青海)、55份商品样本和21份明确储存期1.5年及以上样本的测定,显示80%主产区当归药材中藁本内酯的含量在1.0%以上。研究表明,化学转化法可以间接准确测定当归药材中藁本内酯的含量,可以评价以藁本内酯为主药效成分的中药材(如当归、川芎)或中成药的质量优劣。建议中国药典参照香港中药材标准,规定商品当归药材中藁本内酯的含量不得低于0.6%,不再采用挥发油总量和阿魏酸作为定量检测指标。
关键词:    藁本内酯      化学转化      质量标准      当归      液相色谱     
Development and application of a chemical transformational method for the indirect measurement of ligustilide content in Angelica sinensis
WU Peng-cheng1,2, ZHAO Pan1, LUO Xing-ping3, WANG Yun-jie4, WEI Xiao-ning1, HAO Quan4, LIU Peng-wei5, LIN Rui-li6, NI Lin6, SONG Ping-shun6, LIU Jun-xi1
1. Chinese Academy of Sciences Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China;
2. University of Chinese Academy of Sciences, Beijing 100049, China;
3. School of Chemical Engineering, Northwest Minzu University, Lanzhou 730030, China;
4. Lanzhou Foci Pharmaceutical CO., LTD, Lanzhou 730046, China;
5. Minxian Institute of Angelica sinensis of Gansu Province, Dingxi 748400, China;
6. Gansu Institute for Drug Control, Lanzhou 730000, China
Abstract:
The poor stability of the ligustilide (LIG) makes its quantitation in Angelica sinensis (AS) difficult. This study establishes a chemical conversion method for the determination of ligustilide content in AS and proposes a national pharmacopoeia standard. Mechanical agitation and sonication of a powdered AS extract in a methanol/cyprolamine mixture facilitated the stabilization and transformation of ligustilide. Using an external reference HPLC-DAD method, the cyclopropyl-ligustilide (LIGc) content in the mixture could be determined. The content of ligustilide was greater than 1.0% based on 144 AS specimens including 68 obtained from the originally planted areas of Qinghai and Gansu Province; 55 specimens were obtained from Minxian and Weiyuan County medicine markets, and 21 specimens for which the storage period reached or exceeded 1.5 years. According to the Hong Kong Chinese materis medica standards, the content of ligustilide in AS should not be lower than 0.6%. The developed method could also be applied to the quality control of other Chinese medicinal materials (such as Ligusticum chuanxiong) or Chinese patent medicines in which ligustilide is the main component.
Key words:    ligustilide    chemical conversion    quality standard    Angelica sinensis    liquid chromatography   
收稿日期: 2020-09-15
DOI: 10.16438/j.0513-4870.2020-1484
基金项目: 兰州市人才创新创业项目(2019-RC-19);甘肃省委组织部重点领域人才项目(2019RCXM103);国家自然科学基金面上项目(21672225);科技部中医药现代化研究重点专项项目(2019YFC1711500).
通讯作者: 宋平顺,Tel:86-931-5137121,E-mail:2530517601@qq.com;柳军玺,Tel:86-931-4968212,E-mail:liujx@licp.cas.cn
Email: 2530517601@qq.com;liujx@licp.cas.cn
相关功能
PDF(810KB) Free
打印本文
0
作者相关文章
伍鹏程  在本刊中的所有文章
赵盼  在本刊中的所有文章
罗兴平  在本刊中的所有文章
王云洁  在本刊中的所有文章
魏小宁  在本刊中的所有文章
郝泉  在本刊中的所有文章
刘鹏伟  在本刊中的所有文章
蔺瑞丽  在本刊中的所有文章
倪琳  在本刊中的所有文章
宋平顺  在本刊中的所有文章
柳军玺  在本刊中的所有文章

参考文献:
[1] Chinese Flora Editorial Committee of Chinese Academy of Sciences. Flora of China (中国植物志)[M]. Beijing:Science Press, 1992:41-42.
[2] State Pharmacopoeia Committee. Pharmacopoeia of the People's Republic of China (中华人民共和国药典)[M]. Beijing:China Medical Science Press, 2015:202-203.
[3] Yan H, Zhang XB, Zhu SD, et al. Production regionalization study of Chinese Angelica based on MaxEnt model[J]. China J Tradit Mater Med (中国中药杂志), 2016, 41:3139-3147.
[4] Wang YJ, Yan H, Huang SL, et al. Establishment of HPLC fingerprint and stoichiometry of Angelica sinensis[J]. Chin Tradit Pat Med (中成药), 2020, 42:514-519.
[5] Lin LZ, He XG, Lian LZ, et al. Liquid chromatographic-electrospray mass spectrometric study of the phthalides of Angelica sinensis and chemical changes of Z-ligustilide[J]. J Chromatogr A, 1998, 810:71-79.
[6] Lu GH, Chan K, Liang YZ, et al. Development of high-performance liquid chromatographic fingerprints for distinguishing Chinese Angelica from related Umbelliferae herbs[J]. J Chromatogr A, 2005, 1073:383-392.
[7] Yi LZ, Liang YZ, Wu H, et al. The analysis of Radix Angelicae Sinensis (Danggui)[J]. J Chromatogr A, 2009, 1216:1991-2001.
[8] Nino G, Yang YP, Franz KH, et al. Angelica sinensis (Oliv.) Diels:influence of value chain on quality criteria and marker compounds ferulic acid and Z-ligustilide[J]. Medicines, 2017, 4:1-14.
[9] Hou J, Guo HR, Du T, et al. Quality study of new varieties of Angelicae sinensis in different storage periods based on index compounds and near-infrared spectroscopy[J]. J Chin Med Mater (中药材), 2020, 43:564-568.
[10] Chen J, Zhang Y, Wang HL, et al. Fingerprint and multi-components content determination of standard decoction of Angelicae sinensis Radix[J]. Chin Tradit Herb Drugs (中草药), 2019, 50:4538-4546.
[11] Xu XQ, Chen Bo, Zhang XB, et al. Determination and evaluation of multicomponent content of Angelica sinensis in the main production areas of Gansu by UPLC[J]. Nat Prod Res Dev (天然产物研究与开发), 2020, 32:1014-1022.
[12] Yan ML, Ding GY, Cong LF, et al. Rapid evaluation of vasodilation efficacy of Angelica sinensis by near infrared spectroscopy based on quality markers[J]. Chin Tradit Her Drug (中草药), 2019, 50:4538-4546.
[13] Zhang YX, Zhang YM, Han YM, et al. Pharmacokinetics, tissue distribution, and safety evaluation of a ligustilide derivative (LIGc)[J]. J Pharm Biomed Anal, 2020, 182:113140.
[14] Yan R, Ko NL, Li SL, et al. Pharmacokinetics and metabolism of ligustilide, a major bioactive component in Rhizoma Chuanxiong, in the rat[J]. Drug Metab Dispos, 2008, 36:400-408.
[15] Alejandra L, Mayela DA, Jose LV, et al. Phthalides:distribution in nature, chemical reactivity, synthesis, and biological activity[J]. Prog Chem Org Nat Prod, 2017, 104:127-245.
[16] Zuo AH, Wang L, Xiao HH. Research progress studies on pharmacology and pharmacokinetics of ligustilide[J]. China J Chin Mater Med (中国中药杂志), 2012, 37:13-16.
[17] Zhang LB, Lv JL, Chen H, et al. Research progress of structures and pharmacological activities of phthalides from Angelica sinensis[J]. China J Chin Mater Med (中国中药杂志), 2016, 41:167-176.
[18] Zhao KJ, Dong TX, Tu PF, et al. Molecular genetic and chemical assessment of Radix Angelica (Danggui) in China[J], J Agric Food Chem. 2003, 51:2576-2583.
[19] Zhang XG, Li XR, Wang QL, et al. Study on effects of endophytes on growth and production of Z-Ligustilide and ferulic acid in Angelica sinensis[J]. Braz J Bot, 2016, 39:417-426.
[20] Yan ML, Cong LF, Zhang ZY, et al. Rapid evaluation of anti-inflammatory efficacy of Angelica sinensis (Oliv.) Diels by near infrared spectroscopy based on quality markers[J]. J Instrum Anal (分析测试学报), 2020, 39:1320-1326.
[21] International Organization for Standardization. Traditional Chinese Medicine-Angelica sinensis Root[M]. Switzerland:ISO copyright office, 2019:1-13.
[22] Yang WZ, Zhang YB, Wu WY, et al. Approaches to establish Q-markers for the quality standards of traditional Chinese medicines[J]. Acta Pharm Sin B, 2017, 7:439-446.
[23] Yang WZ, Qiao X, Li K, et al. Identification and differentiation of Panax ginseng, Panax quinquefolium, and Panax notoginseng by monitoring multiple diagnostic chemical markers[J]. Acta Pharm Sin (药学学报), 2016, 51:568-575.
[24] Beck JJ, Stermitz FR. Addition of methyl thioglycolate and benzylamine to (Z)-ligustilide, a bioactive unsaturated lactone constituent of several herbal medicines. An improved synthesis of (Z)-ligustilide[J]. J Nat Prod, 1995, 58:1047-1055.
[25] Zuo AH, Cheng MC, Zhuo RJ, et al. Structure elucidation of degradation products of Z-ligustilide by UPLC-QTOF-MS and NMR spectroscopy[J]. Acta Pharm Sin (药学学报), 2013, 48:911-916.
[26] Pauli GF, Chen SN, Simmler C, et al. Importance of purity evaluation and the potential of quantitative 1H NMR as a purity assay[J]. J Med Chem, 2014, 57:9220-9231.
相关文献:
1.杨帆;肖远胜;章飞芳;薛兴亚;徐青;梁鑫淼.当归化学成分的HPLC-MS/MS分析[J]. 药学学报, 2006,41(11): 1078-1083
2.苏东敏;庾石山;秦海林.当归中新的二聚苯酞衍生物[J]. 药学学报, 2005,40(2): 141-144
3.吴广通;石力夫;胡晋红;李玲.超临界流体萃取法测定川芎中藁本内酯含量的研究[J]. 药学学报, 1998,33(6): 457-460
4.张金兰;何秀峰;周志华.藁本中5种成分的高效液相色谱法测定[J]. 药学学报, 1996,31(8): 622-625