Stress degradation study of Etoricoxib, isolation, and characterization of major degradation impurity by preparative high‐performance liquid chromatography, liquid chromatography‐mass spectrometry, and nuclear magnetic resonance: Validation of ultra‐performance liquid chromatography method

SEPARATION SCIENCE PLUS Pub Date : 2024-01-09 DOI:10.1002/sscp.202300106

Babu Reddy Goguladinne, Pulipaka Shyamala, K. M. V. N. Rao

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Abstract

Etoricoxib (ETO) is a selective cyclooxygenase‐2 inhibitor, used as a nonsteroidal anti‐inflammatory drug. In this study, a detailed investigation was conducted on the degradation behavior of ETO under acidic, basic, neutral, photolytic, oxidative, and thermal degradation conditions as per the International Conference on Harmonization (ICH) guideline Q1A (R2). A gradient “ultra‐performance liquid chromatography (UPLC)” method was developed for separating the degradation products formed under various degradation conditions along with process‐related impurities. Acquity BEH phenyl column was used for the separation of analytes and 0.1% formic acid in water and 0.05% formic acid in acetonitrile:methanol (8:2 %v/v) were used as mobile phase‐A and mobile phase‐B. A major degradant namely, N‐oxide impurity was observed in oxidative degradation along with two minor degradants where N‐oxide was confirmed based on LC‐mass spectrometry (LC‐MS) studies. Further, the major degradant was enriched and isolated using preparative HPLC and the conformation of the N‐oxide impurity was established using nuclear magnetic resonance techniques including two‐dimensional studies and high‐resolution MS. In addition, the method for related substances by UPLC has been validated by considering a major degradant, namely N‐oxide along with process‐related impurities as per the ICH guidelines validation parameters.

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采用制备型高效液相色谱法、液相色谱-质谱法和核磁共振法研究依托考昔的应力降解、主要降解杂质的分离和特征：超高效液相色谱法的验证

依托考昔（ETO）是一种选择性环氧化酶-2 抑制剂，用作非甾体抗炎药。本研究根据国际协调会议（ICH）指南 Q1A (R2)，对 ETO 在酸性、碱性、中性、光解、氧化和热降解条件下的降解行为进行了详细调查。开发了一种梯度 "超高效液相色谱（UPLC）"方法，用于分离在各种降解条件下形成的降解产物以及与工艺相关的杂质。Acquity BEH苯基色谱柱用于分离分析物，0.1%甲酸水溶液和0.05%甲酸乙腈：甲醇（8:2 %v/v）水溶液分别用作流动相A和流动相B。在氧化降解过程中观察到一种主要降解物，即 N-氧化物杂质，以及两种次要降解物，其中 N-氧化物是根据 LC-MS 研究确认的。此外，还利用制备型高效液相色谱法富集和分离了主要降解物，并利用核磁共振技术（包括二维研究和高分辨率质谱）确定了 N-氧化物杂质的构象。此外，还根据 ICH 指南的验证参数，考虑了一种主要降解剂（即 N-氧化物）以及与工艺相关的杂质，验证了通过 UPLC 检测相关物质的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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