ABSTRACT

The present study aimed to separate the three-drug combination and degradant products by applying stress studies in bulk and pharmaceutical using RP-HPLC green analytical chemistry principles to make the separation better and more effective without compromising the standard limits. The three drugs have separated using the Mobile Phase Mixture of 10 volumes of buffer (0.1% triethanolamine in water) and 90 volumes of ethanol on the stationary phase Inertsil ODS 3 (250 mm x 4.6 mm), 5 µm column, at a wavelength of 256 nm. The method has been performed on a linear concentration range of 12–28 µg/mL for ATR, EZB, and 192- 448 µg/mL for FNF. The forced degradation studies showed that the ATR had > 5% degradation in acid, peroxide and thermal degradation, as EZB tends to degrade more than 15% at alkali hydrolysis. Moreover, the methodology has been validated according to ICH Q2 R1 guidelines, assessed using green evaluation tools like GAPI, AES, and AGREE, and found eco-friendly according to the output of the greenness outcomes. The developed method employed for determining three drugs has shown within limits according to the guidelines, easily adaptable by the pharmaceutical industries for their regular quality control analysis of the combinations.

摘要

本研究旨在通过使用 RP-HPLC 绿色分析化学原理在散装和药物中应用压力研究来分离三药组合和降解产物，以便在不影响标准限度的情况下更好、更有效地分离。使用 10 体积缓冲液（0.1% 三乙醇胺水溶液）和 90 体积乙醇的流动相混合物在固定相 Inertsil ODS 3（250 毫米 x 4.6 毫米）、5 µm 色谱柱上分离这三种药物，波长为256 纳米。该方法在 ATR、EZB 的线性浓度范围为 12–28 µg/mL 和 FNF 的线性浓度范围为 192-448 µg/mL 的情况下执行。强制降解研究表明，ATR 在酸、过氧化物和热降解中的降解率 > 5%，而 EZB 在碱水解时倾向于降解超过 15%。而且，该方法已根据 ICH Q2 R1 指南进行了验证，并使用 GAPI、AES 和 AGREE 等绿色评估工具进行了评估，并根据绿色结果的输出发现其对生态环境友好。根据指南，用于确定三种药物的开发方法已显示在限制范围内，制药行业很容易将其用于对组合进行定期质量控制分析。