张寒;李振皓;范骁辉;
ZHANG Han;LI Zhen-hao;FAN Xiao-hui;Graduate College,Tianjin University of Traditional Chinese Medicine;Department of Chinese Medical Science and Engineering,College of Pharmaceutical Science,Zhejiang University;

• 1:天津中医药大学研究生院
• 2:浙江大学药学院中药科学与工程学系

摘要(Abstract)：

化学标志物检验分析已经成为当前中药质量评价的主流策略,但如何兼顾评价方法的准确性和整体性仍是一大难题。该研究以丹参注射液为载体,将指纹图谱与一标多测相结合,采用超高效液相色谱(UPLC)建立了其定量指纹图谱,以期充分发挥各自方法的优势,为更全面、快捷地评价丹参注射液产品质量提供技术支撑。所建UPLC指纹图谱包含13个共有峰,其中11个峰用超高效液相色谱-四极杆-飞行时间串联质谱(UPLC-QTOF-MS)进行了指认;进一步以丹参素钠为内参物,通过斜率法确定了原儿茶醛、咖啡酸、迷迭香酸、紫草酸、丹酚酸B的相对校正因子,采用一标多测法建立了这6个成分的含量测定方法。采用该方法测定了12个批次的丹参注射液,样品指纹图谱与对照图谱的相似度均大于0. 99,批间一致性良好;比较一标多测法所得6个成分的含量与外标法的测量值,RSD均小于4. 3%,表明该方法准确度良好。该研究建立的一标多测UPLC定量指纹图谱可在只消耗对照品丹参素钠的情况下,较全面地反映丹参注射液的内在质量,检测成本和检测时间均大幅降低,为进一步提升丹参注射液质量标准提供了技术依据。
Testing and analysis of chemical markers is currently the prevailing approach for quality assessment of traditional Chinese medicines. However,several important issues remain to be addressed,including the trade-off between accuracy and coverage. In this study,in order to give full play to the advantages of their respective methods and provide technical support for more comprehensively and rapidly evaluate the quality of Danshen Injection products,a fingerprint method was coupled with quantitative analysis of multicomponents by single marker( QAMS),with Danshen Injection as the carrier. Ultra performance liquid chromatography( UPLC) was used to establish the quantitative fingerprint. The UPLC fingerprints contained 13 common peaks,11 of which were identified by using ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-QTOF-MS). Furthermore,with sodium danshensu as the internal reference substance,relative correction factors( RCFs) of protocatechuic aldehyde,caffeic acid,rosmarinic acid,lithospermic acid,and salvianolic acid B were calculated through slope analysis method,and the QAMS method was adopted to determine the contents of these 6 components. The UPLC fingerprint was employed to assess the consistency of 12 batches of Danshen Injection,which showed good batch-to-batch consistency with similarity higher than 0. 99. In the comparison of contents of the six constituents obtained by QAMS and external standard method( ESM),RSD was all less than 4. 3%,indicating the good accuracy of the QAMS method. The QAMS method developed in this study combined with UPLC fingerprint can comprehensively reflect the internal quality of Danshen Injection when only the reference substance sodium danshensu is consumed,with greatly reduced detection cost and time. It provides a technical basis for further improving the quality standard of Danshen Injection.

关键词(KeyWords)： 丹参注射液;UPLC;定量指纹图谱;一标多测
Danshen Injection;UPLC;quantitative fingerprint;QAMS

Abstract:

Keywords:

基金项目(Foundation): 国家“重大新药创制”科技重大专项(2018ZX09201011);; 国家自然科学基金青年基金项目(81803714)

作者(Author): 张寒;李振皓;范骁辉;
ZHANG Han;LI Zhen-hao;FAN Xiao-hui;Graduate College,Tianjin University of Traditional Chinese Medicine;Department of Chinese Medical Science and Engineering,College of Pharmaceutical Science,Zhejiang University;

Email:

DOI: 10.19540/j.cnki.cjcmm.20190410.310

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