基于紫外光谱的中药生产过程全局预测模型的构建和验证

Development and validation of global prediction models for monitoring the manufacturing process of herbal medicine by ultraviolet spectroscopy

目的:中药制剂的过程监控是保证产品质量的必要手段。典型的中药制药过程由多个操作单元组成,例如醇沉、浓缩和水沉等。与传统的一个操作单元建立一个预测模型的做法相比,全局模型覆盖了制药过程中各个操作单元样本的变异情况,可用于各子步骤中间产物的监测。方法:采用紫外光谱法建立典型中药制剂丹红注射液的全局模型。以丹参素、原儿茶醛、迷迭香酸、丹酚酸A、丹酚酸B、羟基红花黄色素A、总糖、总酚的含量为指标,建立了基于紫外光谱的丹红注射剂中间体的多指标快速分析方法。将丹红注射液不同操作单元的中间体进行随机混合以引入更多的变异,获得具有代表性的样本集。采用准确度轮廓对建立的紫外光谱快速分析方法进行全面的验证。结果:所建模型具有较高的决定系数,且具有较低的验证集均方根误差。所选择的指标中有5个指标通过了所有验证,其中总糖分析模型效果较差,不适合用于过程检测。结论:本研究表明,基于紫外光谱的全局模型可以对丹红注射液制备过程中酚酸类物质进行定量分析,且该方法简单、快速、无损。

Objective: Process monitoring for traditional Chinese medicine(TCM) preparations is necessary to ensure the quality of the product. A typical pharmaceutical process of TCM preparations consists of multiple manufacturing units, such as ethanol precipitation, concentration, and water precipitation, among others. Compared with the traditional practice of one prediction model for one unit, the global model covers the variation from samples with different backgrounds or processes and can be used to monitor intermediates from substeps.Methods: We used ultraviolet(UV) spectroscopy to establish global models for a typical TCM preparation-Danhong injection.The concentrations of danshensu, protocatechualdehyde, rosmarinic acid, salvianolic acid A, salvianolic acid B, and hydroxyl safflor yellow A and the total phenolic and total sugar contents were quantified for every intermediate from operation units of Danhong injection. New samples prepared by mixing different intermediates were introduced for the calibration set to cover more variations. An accuracy profile was employed to validate the developed method from the aspects of specificity, trueness, precision,accuracy, linearity, and robustness.Results: The developed models showed a high determination coefficient(R2) value up to 0.97 and a low root-mean-square error of the prediction set. Five components of the models passed all validation tests, whereas the total sugar was not suitable for modeling with UV and did not apply to the whole process.Conclusions: This study indicates that the global models of UV spectroscopy for the quantitative determination of phenolic acids are feasible and reliable with a simple, rapid, and non-destructive method.Graphical abstract: http://links.lww.com/AHM/A22.