开发抗体药物联体的分析离子交换色谱方法,其中含有易于水解的苏胺-乙烯联结化学物质
Jessica Webb1, Chendi Niu1, Benjamin Ritter1
1Department of Analytical Sciences, AstraZeneca, One Medimmune Way, Gaithersburg, MD, 20878, USA.
Journal of pharmaceutical sciences
|August 25, 2024
概括
开发针对抗体药物联合体 (ADC) 的充电试验是具有挑战性的,因为水解. 两种方法,高pH化和子单位分析,成功地解决了水解异质性,以准确评估ADC电荷变异.
科学领域:
- 生物化学 生物化学
- 分析化学 分析化学
- 蛋白质治疗药物 蛋白质治疗药物
背景情况:
- 电荷变异是抗体药物合物 (ADC) 的关键质量属性.
- 在ADC中,乳胺-硫乙烯结合化学可以导致水解,产生酸性峰值,使电荷分析复杂化.
- 这种水解异质性可以掩盖ADC中的其他重要的电荷变化.
研究的目的:
- 为了应对具有易于水解的结合ADC的电荷测试开发的挑战.
- 研究解决ADC中的水解异质性的方法.
- 为了确保对ADC充电变体的准确评估.
主要方法:
- 研究了具有易于水解的顺丁胺 - 硫乙烯结合的工程ADC.
- 方法1:在高pH条件下化ADC以驱动完整的水解.
- 方法2:在IdeS消化后,在子单元级别分析电荷变量.
主要成果:
- 无论是高pH化方法还是IdeS消化方法,都为ADCs产生了可接受的电荷配置.
- 使用这两种方法成功获得了定量整合结果.
- 这些方法有效地解决了水解异质性的掩盖效应.
结论:
- 两种不同的方法得到了验证,用于在具有水解问题的ADC中准确分析电荷变异.
- 这些策略使ADC质量属性的可靠表征成为可能.
- 这些发现支持ADC开发和制造的强有力的质量控制.
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