Quality by design (QbD) refers to the achievement of certain predictable quality with desired and predetermined specifications. A quality-by-design approach to method development can potentially lead to a more robust/rugged method due to emphasis on risk assessment and management than traditional or conventional approach. An important component of the QbD is the understanding of dependent variables, various factors, and their interaction effects by a desired set of experiments on the responses to be analyzed. The present study describes the risk based HPLC method development and validation of ceftriaxone sodium in pharmaceutical dosage form. An efficient experimental design based on central composite design of two key components of the RP-HPLC method (mobile phase and pH) is presented. The chromatographic conditions were optimized with the Design Expert software 11.0 version, i.e., Phenomenex ODS column C18 (250 mm × 4.6 mm, 5.0 μ), mobile phase used acetonitrile to water (0.01% triethylamine with pH 6.5) (70:30, v/v), and the flow rate was 1 ml/min with retention time 4.15 min. The developed method was found to be linear with r2 = 0.991 for range of 10–200 μg/ml at 270 nm detection wavelength. The system suitability test parameters, tailing factor and theoretical plates, were found to be 1.49 and 5236. The % RSD for intraday and inter day precision was found to be 0.70–0.94 and 0.55–0.95 respectively. The robustness values were less than 2%. The assay was found to be 99.73 ± 0.61%. The results of chromatographic peak purity indicate the absence of any coeluting peaks with the ceftriaxone sodium peak. The method validation parameters were in the prescribed limit as per ICH guidelines. The central composite design experimental design describes the interrelationships of mobile phase and pH at three different level and responses to be observed were retention time, theoretical plates, and peak asymmetry with the help of the Design Expert 11.0 version. Here, a better understanding of the factors that influence chromatographic separation with greater confidence in the ability of the developed HPLC method to meet their intended purposes is done. The QbD approach to analytical method development was used for better understanding of method variables with different levels.

中文翻译：

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头孢曲松钠 HPLC 方法开发和验证的 QbD 方法

质量源于设计 (QbD) 是指以期望的和预定的规格实现某些可预测的质量。与传统或传统方法相比，由于强调风险评估和管理，方法开发的质量源于设计方法可能会导致更稳健/坚固的方法。QbD 的一个重要组成部分是通过对要分析的响应进行所需的一组实验来了解因变量、各种因素及其相互作用。本研究描述了药物剂型中头孢曲松钠的基于风险的 HPLC 方法开发和验证。提出了一种基于 RP-HPLC 方法（流动相和 pH 值）的两个关键组成部分的中心复合设计的高效实验设计。使用Design Expert软件11.0版优化色谱条件，即Phenomenex ODS柱C18（250 mm × 4.6 mm，5.0 μ），流动相使用乙腈至水（0.01%三乙胺，pH 6.5）（70:30，v /v)，流速为 1 ml/min，保留时间为 4.15 min。发现所开发的方法在 270 nm 检测波长下在 10–200 μg/ml 范围内与 r2 = 0.991 呈线性关系。系统适用性测试参数、拖尾因子和理论塔板数分别为 1.49 和 5236。日内和日间精密度的 % RSD 分别为 0.70-0.94 和 0.55-0.95。稳健性值小于 2%。测定结果为 99.73 ± 0.61%。色谱峰纯度的结果表明没有任何与头孢曲松钠峰共流出的峰。根据 ICH 指南，方法验证参数在规定的限度内。中心复合设计实验设计在 Design Expert 11.0 版本的帮助下描述了流动相和 pH 在三个不同水平上的相互关系，并且要观察的响应包括保留时间、理论塔板数和峰不对称性。在这里，可以更好地了解影响色谱分离的因素，并对开发的 HPLC 方法满足其预期目的的能力更有信心。分析方法开发的 QbD 方法用于更好地理解不同水平的方法变量。中心复合设计实验设计在 Design Expert 11.0 版本的帮助下描述了流动相和 pH 在三个不同水平上的相互关系，并且要观察的响应包括保留时间、理论塔板数和峰不对称性。在这里，可以更好地了解影响色谱分离的因素，并对开发的 HPLC 方法满足其预期目的的能力更有信心。分析方法开发的 QbD 方法用于更好地理解不同水平的方法变量。中心复合设计实验设计在 Design Expert 11.0 版本的帮助下描述了流动相和 pH 在三个不同水平上的相互关系，并且要观察的响应包括保留时间、理论塔板数和峰不对称性。在这里，可以更好地了解影响色谱分离的因素，并对开发的 HPLC 方法满足其预期目的的能力更有信心。分析方法开发的 QbD 方法用于更好地理解不同水平的方法变量。对影响色谱分离的因素有了更好的了解，并对开发的 HPLC 方法满足其预期目的的能力更有信心。分析方法开发的 QbD 方法用于更好地理解不同水平的方法变量。对影响色谱分离的因素有了更好的了解，并对开发的 HPLC 方法满足其预期目的的能力更有信心。分析方法开发的 QbD 方法用于更好地理解不同水平的方法变量。