Robustness evaluation of weak anion exchange chromatography method for the purity analysis of therapeutic oligonucleotides

IF 3.8 2区化学 Q1 BIOCHEMICAL RESEARCH METHODS

Journal of Chromatography A Pub Date : 2024-09-30 DOI:10.1016/j.chroma.2024.465412

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Abstract

Therapeutic oligonucleotides are becoming an important class of therapeutics. Their manufacturing processes can result in the formation of impurities, particularly truncated species. To ensure the quality and safety of the product, it is crucial to evaluate the presence of these species. Liquid chromatography analysis enables such purity determination. In this context, a recently described weak anion exchange chromatography method was optimized to allow the effective separation of different impurities. The optimization addressed the complexity and instability of the mobile phases, which contained salts and organic compounds. Adjustments were made to the mobile phase composition and gradient to meet the requirements of QC laboratories. Additionally, to ensure the method's reliability, a robustness study was conducted based on a risk assessment. Five factors were considered potential risks and were assessed experimentally on different chromatographic outputs. This led to the definition of a robust space, ensuring the method's reliability for the purity determination of oligonucleotides.

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用于治疗性寡核苷酸纯度分析的弱阴离子交换色谱法的稳健性评估。

治疗性寡核苷酸正在成为一类重要的治疗药物。其生产过程会产生杂质，尤其是截短的核苷酸。为确保产品的质量和安全性，评估这些物种的存在至关重要。液相色谱分析可以进行此类纯度测定。在这种情况下，对最近描述的弱阴离子交换色谱法进行了优化，以有效分离不同的杂质。这次优化解决了流动相的复杂性和不稳定性问题，流动相中含有盐和有机化合物。对流动相成分和梯度进行了调整，以满足质量控制实验室的要求。此外，为确保该方法的可靠性，还在风险评估的基础上进行了稳健性研究。五个因素被视为潜在风险，并在不同的色谱结果上进行了实验评估。最终确定了稳健空间，确保了寡核苷酸纯度测定方法的可靠性。

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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来源期刊

Journal of Chromatography A 化学-分析化学

CiteScore

7.90

自引率

14.60%

发文量

742

审稿时长

45 days

期刊介绍： The Journal of Chromatography A provides a forum for the publication of original research and critical reviews on all aspects of fundamental and applied separation science. The scope of the journal includes chromatography and related techniques, electromigration techniques (e.g. electrophoresis, electrochromatography), hyphenated and other multi-dimensional techniques, sample preparation, and detection methods such as mass spectrometry. Contributions consist mainly of research papers dealing with the theory of separation methods, instrumental developments and analytical and preparative applications of general interest.