基于QbD理念的三七总皂苷定量分析方法持续改进研究

该文提出基于质量源于设计(QbD)的中药分析方法持续改进策略。以三七总皂苷(PNS)5种皂苷类成分的超高效液相色谱(UPLC)定量分析方法开发为例,完成分析方法从HPLC到UPLC的转换。在UPLC开发中,采用Plackett-Burman设计和Box-Behnken设计理解关键方法参数(CMP)与关键方法属性(CMA)之间的关系,建立贝叶斯概率设计空间;优选稳健色谱条件为初始乙腈20%,等度时间10 min,梯度变化速率6%·min~(-1),分析时间17 min,采用Accuracy profile进行方法学验证。在相同的分析目标(ATP)下,从色谱条件、CMP辨识结果、CMP-CMA关系模型、系统适用性等方面对PNS的HPLC和UPLC定量分析性能的一致性进行比较,结果表明UPLC可缩短分析时间、提高关键峰对分离度、色谱系统适用性满足要求,UPLC可替代HPLC进行PNS定量分析。

Continual improvement of quantitative analytical method development of Panax notogineng saponins based on quality by design

This study is aimed to propose a continual improvement strategy based on quality by design (QbD). An ultra high performance liquid chromatography (UPLC) method was developed to accomplish the method transformation from HPLC to UPLC of Panax notogineng saponins (PNS) and achieve the continual improvement of PNS based on QbD, for example. Plackett-Burman screening design and Box-Behnken optimization design were employed to further understand the relationship between the critical method parameters (CMPs) and critical method attributes (CMAs). And then the Bayesian design space was built. The separation degree of the critical peaks (ginsenoside Rg₁ and ginsenoside Re) was over 2.0 and the analysis time was less than 17 min by a method chosen from the design space with 20% of the initial concentration of the acetonitrile, 10 min of the isocratic time and 6%·min^-1 of the gradient slope. At last, the optimum method was validated by accuracy profile. Based on the same analytical target profile (ATP), the comparison of HPLC and UPLC including chromatograph method, CMA identification, CMP-CMA model and system suitability test (SST) indicated that the UPLC method could shorten the analysis time, improve the critical separation and satisfy the requirement of the SST. In all, HPLC method could be replaced by UPLC for the quantity analysis of PNS.