Abstract A binary mixture of Lesinurad (LES) and Allopurinol (ALP) is a newly marketed anti-gout combination where no stability indicating methods have been reported for its analysis. In this work, a simple, green stability indicating capillary zone electrophoretic method coupled with a diode array detector (CZE-DAD) has developed and validated for analyzing this mixture in their combined dosage form. Separation was achieved using fused silica capillary (55 cm × 50 μm id) using 50 mM borate buffer adjusted to pH 10 with 0.5 M NaOH. The linearity concentration ranges were 5–50 and 10–100 μg/mL for LES and ALP, respectively. The stability indicating ability of the proposed method was investigated by analyzing the two drugs after being subjected to several stress conditions as per ICH guidelines. The developed method was able to separate the two intact drugs from their degradation products formed under different stress conditions (acidic, basic, oxidation). In addition, the developed method has been applied to investigate the degradation kinetics of LES and ALP under acidic, basic and oxidative conditions. The degradation of the two drugs was found to follow pseudo-first order kinetics and degradation half-lives were also calculated for both drugs under different stress conditions. The developed CZE method is the first in the literature for determination of both LES and ALP in the presence of their related degradation products with high separation efficiency, minimum solvent consumption, enhanced method greenness and low operation cost. Thus, the proposed method is an efficient simple eco- friendly analytical tool for the routine analysis of LES and ALP in their combined dosage form in presence of their degradation products in quality control laboratories.

中文翻译：

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绿色稳定性指示毛细管电泳法同时测定片剂剂型中的来西乐和别嘌呤醇：降解动力学研究

摘要 Lesinurad (LES) 和别嘌呤醇 (ALP) 的二元混合物是一种新上市的抗痛风组合，尚未报告其分析稳定性指示方法。在这项工作中，开发并验证了一种简单的绿色稳定性指示毛细管区带电泳方法与二极管阵列检测器 (CZE-DAD) 相结合，用于分析组合剂型中的这种混合物。使用熔融石英毛细管（55 cm × 50 μm 内径）使用 50 mM 硼酸盐缓冲液（用 0.5 M NaOH 调节至 pH 值 10）实现分离。LES 和 ALP 的线性浓度范围分别为 5–50 和 10–100 μg/mL。根据 ICH 指南，通过在经受多种压力条件后对两种药物进行分析，研究了所提出方法的稳定性指示能力。开发的方法能够将两种完整的药物与其在不同应激条件（酸性、碱性、氧化）下形成的降解产物分离。此外，所开发的方法已用于研究酸性、碱性和氧化条件下 LES 和 ALP 的降解动力学。发现两种药物的降解遵循伪一级动力学，还计算了两种药物在不同压力条件下的降解半衰期。开发的 CZE 方法是文献中第一个在 LES 和 ALP 存在相关降解产物的情况下测定 LES 和 ALP 的方法，具有高分离效率、最少的溶剂消耗、增强的方法绿色和低运行成本。因此，