Purpose

The chromatography methods such as HPLC, HPTLC etc. were developed for simultaneous estimation of multiple fixed-dose combination products of metformin hydrochloride which need single chromatography condition to save solvent consumption. The method was developed by the implementation of analytical quality by design approach based on principles of quality risk management (QRM) and design of experiments (DoE) as per regulatory requirements.

Methods

QRM was applied for the analysis of twenty potential method risk parameters using the Ishikawa diagram and quality risk assessment according to ICH Q9 guideline. DoE was applied by Taguchi OA screening design and Box-Behnken response surface analysis method. Method operable design range was navigated for optimisation of critical method risk parameters as per the analytical target profile for development of the method. The developed method was applied for the analysis of three different fixed-dose combination products of metformin hydrochloride.

Results

By the QRM process, seven method risk parameters were found critical for the development of the method. After the Taguchi screening design, the main effect of mobile phase composition, %w/v of ammonium acetate and saturation time was found to be significant. The results of the Box-Behnken design showed a quadratic relationship between CMPs and CMAs. The developed method was found to be specific, accurate and precise. The results of the assay were found in good agreement with the labelled claim.

Conclusion

The developed method can analyse three different fixed-dose combination products of metformin hydrochloride which required three different chromatography methods. Hence, the method is versatile and eco-friendly.

中文翻译：

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基于质量风险管理的分析质量：环保，多功能色谱方法的设计方法，可同时估算多种抗糖尿病药物固定剂量组合产品

目的

开发了HPLC，HPTLC等色谱方法，用于同时估算盐酸二甲双胍的多种固定剂量联合产品，这些产品需要单一色谱条件即可节省溶剂消耗。该方法是通过根据质量风险管理（QRM）原则和设计要求（DoE）根据监管要求通过设计方法实施分析质量而开发的。

方法

根据ICH Q9指南，使用石川图和质量风险评估将QRM应用于20种潜在方法风险参数的分析。通过田口OA筛选设计和Box-Behnken响应面分析方法应用DoE。导航方法可操作的设计范围，以根据分析方法的目标配置文件优化关键方法风险参数。所开发的方法用于分析盐酸二甲双胍的三种不同固定剂量组合产物。

结果

通过QRM流程，发现七个方法风险参数对于方法的开发至关重要。经过Taguchi筛选设计后，发现流动相组成，乙酸铵的％w / v和饱和时间的主要影响是显着的。Box-Behnken设计的结果表明CMP和CMA之间存在二次关系。发现所开发的方法是特定，准确和精确的。发现测定结果与标记的权利要求非常一致。

结论

所开发的方法可以分析三种需要两种色谱方法的盐酸二甲双胍固定剂量组合产物。因此，该方法是通用且环保的。