中药整体质量评价中一种新的替代对照品技术“双标多测法”的建立研究

Due to the complexity of components in traditional Chinese medicines (TCMs), it is the best way to establish method for the effective quality control of TCMs using multi-components analysis. However, the limited availability and high cost of reference substances hinders the wide popularization for routine quality control of TCMs. The "substitute reference substance" method and "quantitative analysis of multi-components by single marker" are both worth considering for resolving the problem. In the two methods, the content of each component could be calculated by relative correction factor and using relative retention time for chromatographic peak identification, but the accuracy and repeatability of quantitative analysis and peak identification are not good enough. A new high-performance liquid chromatography method on substitute reference substance for multi-components assay named two reference substances for determination of multiple components was established, using relative correction factor focus on detection wavelength for quantitative analysis and linear calibration using two reference substances for peak identification. It has been demonstrated that the new method is more accurate than the two methods mentioned above by validation experiments. In this study, we select olibanum and rhubarb as research materials, and carry out comprehensive experiments on two reference substances for determination of multiple components to solve the key problem of substitute reference substance for wide application.

由于中药成分复杂,采用多指标含量测定法方能全面地控制其质量，但对照品制备和提供困难，且价格昂贵，极大地限制了该法在质量标准中的推广应用。替代对照品法或一测多评法是较好的解决方案。这类方法使用1个对照品对多个成分进行含量测定，以相对校正因子法定量，相对保留时间法定性，但误差常常偏大。本课题提出了一种新的替代对照品模式的多指标含量测定技术--双标多测法，以检测波长为核心的相对校正因子法定量，以双标线性校正法定性色谱峰，定量、定性效果明显优于现有替代模式方法。本课题将以乳香和大黄两个药材为研究对象，在更复杂药材基质中、更复杂色谱条件下、更多色谱柱(≥50)情况下，全面深入研究双标多测法，以期解决替代对照品模式实用化的关键问题，推动多指标含量测定技术在中药质量评价中的应用。

课题组研究开发了双标多测法，该法基于检测波长为核心的相对校正因子法定量，基于双标线性校正技术的色谱峰定性法，其定量、定性效果明显优于现有替代模式方法。并在此基础上开发了结合双标线性校正法、PDA光谱和质谱三种方法的色谱峰定性方法的配套的软件，采用该软件进行替代对照品模式的色谱峰定性，其准确度和重现性优于目前的各种技术。该研究顺应了药品标准物质的数字化潮流，减少实物标准物质的制备与标定，推动替代对照品法在中药综合质量控制和化学药有关物质检查中的应用。