对微柱阵列列的评价,用于分离基化寡核酸及其二聚体
Lieve Dillen1, Tiny Deschrijver2, Kurt Van Mol3
1Drug Metabolism and Pharmacokinetics Janssen R&D Beerse Belgium.
Analytical science advances
|May 8, 2024
概括
离子对逆相色谱在微柱阵列列上有效分离治疗性寡核酸. 优化的移动相可以分解二聚体,这对于分析复杂的寡核酸杂质和候选药物至关重要.
科学领域:
- 分析化学 分析化学
- 生物化学 生化学
- 制药科学 制药科学
背景情况:
- 治疗性寡核酸分析因酸酸键中的杂质和性中心而复杂.
- 现有的染色学方法在解决密切相关的寡核酸物种方面扎.
研究的目的:
- 为了研究使用微柱阵列列的寡核酸的离子对逆相色谱 (IP-RP-C).
- 评估不同移动相条件对寡核酸分离和二聚体选择性的影响.
主要方法:
- 在新型微柱阵列列上使用IP-RP-C进行寡核酸分析.
- 测试了两个移动相系统:三乙烯胺/六化异醇和三乙烯氨酸.
- 分析了16-mer和19-mer治疗性寡核酸模仿物,具有不同的酸链接和修饰.
主要成果:
- 一个移动相抑制了二聚体选择性,显示了更多酸键的增加保留.
- 另一种移动相 (三乙氨酸) 清晰地分解了19-mer RNA模拟的二聚体,将所有16种理论异构体分离出来.
- 微柱阵列列显示出更好的分离能力,用于具有挑战性的寡核酸分析.
结论:
- 微柱阵列列为难以分离的寡核酸提供了有价值的替代方案.
- 优化的移动相对于实现所需的选择性至关重要,特别是对于分立体的分解.
- 这种方法增强了治疗性寡核酸的分析,有助于杂质分析和质量控制.
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