基于分析质量源于设计理念的大补阴丸(浓缩丸)定量指纹图谱方法开发

Development of a Quantitative Fingerprint Method for Dabuyin Pills (concentrated pills) Based on the Analytical Quality by Design Concept

关键词:  大补阴丸(浓缩丸)  分析质量源于设计  确定性筛选试验设计  方法可操作设计区域  高效液相色谱  定量指纹图谱

Key words:  Dabuyin Pills (concentrated pills)  analytical quality by design  definitive screening design  method operable design region  high performance liquid chromatography  quantitative fingerprinting

摘要:

目的 采用分析质量源于设计理念,以高效液相色谱-紫外检测技术建立了大补阴丸(浓缩丸)中5-羟甲基糠醛、3-O-阿魏酰奎尼酸、新芒果苷和盐酸小檗碱4种成分的定量指纹图谱分析方法。方法 首先,确定潜在的关键方法参数(CMPs),然后通过确定性筛选设计辨识关键质量属性(CQAs),再采用逐步回归法建立CMPs与CQAs之间的定量关系模型。采用蒙特卡罗法建立了方法可操作设计区域(MODR)并成功验证。用Plackett-Burman设计评价分析方法的耐用性。结果 用高分辨质谱推断了指纹图谱中9个共有峰对应的化合物,依次为没食子酸、5-羟甲基糠醛、3-O-没食子酸、3-O-阿魏酰奎尼酸、3,5-O-二咖啡酰奎宁酸甲酯、新芒果苷、绿原酸甲酯、芒果苷、盐酸小檗碱。不同批次大补阴丸(浓缩丸)之间、各批次与对照指纹图谱的相似度均大于0.95,表明各批次大补阴丸(浓缩丸)的一致性良好。结论 该方法耐用性良好并通过方法学验证,可用于大补阴丸(浓缩丸)中4种成分含量的测定。

Abstract:

ABSTRACT: OBJECTIVE Using the concept of Analytical Quality by Design, a quantitative fingerprint analysis method for four components (5-hydroxymethylfurfural, 3-O-feruloylquinic acid, neomangiferin, and berberine hydrochloride) in Dabuyin Pills (concentrated pills) was established using high performance liquid chromatography-ultraviolet detection technology. METHODS Firstly, potential critical method parameters (CMPs) were identified. Then, critical quality attributes (CQAs) were distinguished through definitive screening design. Subsequently, quantitative relationship models between CMPs and CQAs were established using stepwise regression . The method operable design region (MODR) was established by the Monte Carlo method and successfully verified. The robustness of the analytical method was evaluated using the Plackett-Burman design. RESULTS Nine common peaks in the fingerprint were identified as their corresponding compounds using high-resolution mass spectrometry (HRMS), which are gallic acid, 5-hydroxymethylfurfural, 3-O-galloylquinic acid, 3-O-feruloylquinic acid, methyl 3,5-O-dicaffeoylquinate, neomangiferin, methyl chlorogenate, mangiferin, and berberine hydrochloride in sequence.The similarity values between different batches of Dabu Yin Wan (Concentrated Pills) and between each batch and the reference fingerprint were all greater than 0.95, indicating that the consistency among different batches of Dabu Yin Wan (Concentrated Pills) is good. CONCLUSION This method has good durability and has been verified by methodology, and can be used for the determination of the contents of 4 components in Dabu Yin Wan (Concentrated Pills).