注射用丹参多酚酸稳定性研究及其稳定性指示性分析方法的建立

目的:研究注射用丹参多酚酸降解产物并建立其稳定性指示性分析方法。方法:采用UPLC-Q-TOF-MS/MS对注射用丹参多酚酸的主要成分进行定性研究,建立可同时测定注射用丹参多酚酸原成分及其降解产物的稳定性指示性分析方法;系统考察注射用丹参多酚酸主要成分在高温、氧化、金属离子、光照等物理化学条件下的稳定性。结果:共鉴定了注射用丹参多酚酸中13个主要活性成分并进行峰面积半定量分析;注射用丹参多酚酸在高温、氧化、三价金属离子条件下均不稳定;在高温、氧化、光照、三价离子和二价离子条件下分别新增降解产物6,4,3,4,1个。所建立的稳定性指示性分析方法能同时测定注射用丹参多酚酸中主要成分及其活性成分的降解产物,分离效果良好。结论:推测注射用丹参多酚酸中主要成分降解机制为大分子多元酚酸类化合物通过苯并呋喃开环、酯键的水解、脱去丹参素等一系列反应降解成如丹参素、原儿茶醛等小分子成分。所建立的稳定性指示性分析方法可用于中药注射剂注射用丹参多酚酸稳定性质量控制。

Study on Stability of Salvianolate Lyophilized Injection and Establishment of Stability-Indicating Analysis Method

Objective: To study the degradation of salvianolate lyophilized injection (SLI) and establish a stability-indicating analysis method. Method: UPLC-Q-TOF-MS/MS was used to conduct a qualitative study on the main components of SLI, and a stability-indicating analysis method was established for simultaneous determination of the original components of SLI and its degradation products. The stability of SLI were systematically assessed under physicochemical conditions of high temperature,oxidation,metal ions. Result: Totally 13 main active ingredients in SLI were identified, and a semi-quantitative analysis was performed. Under the conditions of high temperature,oxidation,light,trivalent ion and divalent ion,6,4,3,4 and 1 new degradation products were added respectively. The established stability-indicating analysis method can simultaneously determine the degradation products of the main components and their active components in SLI, with a good separation effect. Conclusion: According to the degradation mechanism of the main ingredients in SLI, macromolecular polyphenol acid compounds are degraded into small molecular compounds, such as tanshinol and protocatechu aldehyde by a series of reactions, like benzofuran open-loop,hydrolysis of ester bond and removal of DSS. The stability-indicating analysis method can be used for the stability quality control of traditional Chinese medicine Salvianolate Lyophilized Injection (SLI).