使用MALDI-TOF-MS开发生物制剂的高通量糖化选方法.
Weilong Zhang1, Liqi Xie2, Huijuan Zhao1
1NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Communications chemistry
|October 2, 2025
概括
本研究介绍了一种使用MALDI-TOF-MS和内部标准的治疗性蛋白质的快速,高通量糖化分析方法. 优化的方法确保了生物制剂的精确质量控制,增强了生物制药的开发.
科学领域:
- 生物化学 生物化学
- 分析化学 分析化学
- 生物技术是生物技术.
背景情况:
- 糖化对治疗性蛋白质的功能和有效性至关重要.
- 目前用于糖化分析的分析方法缺乏现代生物制药质量控制所需的速度和吞吐量.
研究的目的:
- 开发和验证一种优化,快速和高通量方法,用于治疗性蛋白质的糖化分析.
- 为生物制药制造业的质量控制提供强大的解决方案.
主要方法:
- 结合矩阵辅助激光脱/电离-飞行时间质谱学 (MALDI-TOF-MS) 采用全糖体内部标准方法.
- 开发了一种96井板兼容的方法,允许对每次实验至少192个样本进行分析.
- 验证了治疗蛋白质的方法,如trastuzumab和融合蛋白 (EPO).
主要成果:
- 在trastuzumab分析中获得了高精度 (CV ~10%) 和广泛的线性 (R2 > 0.99).
- 在资格研究中表现出极好的线性,可重复性和稳定性.
- 在具有多个糖化位点的融合蛋白质上成功分析了复杂的甘氨酸结构.
结论:
- 优化的方法为生物制药质量控制中的快速,高吞吐量甘化分析提供了一个非常有前途的解决方案.
- 该方法适用于各种应用,包括克隆选择,批量一致性和生物类似物评估.
- 这种方法显著有利于在糖化生物制剂中对N-甘氨酸的表征.
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