药物开发中的统一色谱:利用杂热盐/宇宙热盐来加速方法开发
Gioacchino Luca Losacco1, Zachary S Breitbach1, Paul L Walsh1
1Analytical Research and Development, Small Molecule CMC Development, AbbVie, Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA.
统一色谱 (UC) 通过使用具有超临界CO2 (scCO2) 的新增剂简化了方法开发. 这种方法增强了分离,并为药物开发的传统方法提供了优越的替代方案.
科学领域:
- 分析化学 分析化学
- 染色体学 染色体学 是一种染色学.
背景情况:
- 超临界流体染色学 (SFC) 已经与统一染色学 (UC) 演变,使得超临界和液态之间的过渡成为可能.
- UC提供了SFC和液体染色学的综合优势,但需要为工业应用开发简化方法.
研究的目的:
- 为UC引入简化方法开发程序.
- 探索新型杂热/大热添加剂在SFC/UC.中的影响.
- 为了证明UC在挑战分离和药物开发方面的实用性.
主要方法:
- 开发一种新的,快速的UC方法开发协议.
- 移动相性质的研究,包括液体修饰剂百分比和含水量.
- 使用的添加剂包括NaClO4 (高热性),HCOONa (高热性) 和NaOMs (混合性).
主要成果:
- 成功地应用UC用于分离核酸,核酸,醇,醇和相关化合物.
- 在加速稳定下,证明了UC在分析AbbVie管道化合物的有效性.
- 使用NaClO4的UC在保留和除降解产品方面表现优于RP-HPLC.
结论:
- 新型添加剂和简化程序提高了UC在工业药物开发中的适用性.
- 在复杂的分离过程中,UC提供了一种强大的工具,比传统方法更有优势.
- UC,特别是含有NaClO4等添加剂的UC,在稳定性研究和杂质分析方面显示出重大前景.
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