| 冯蕊,马陶陶.重组全人抗PD-L1单克隆抗体N糖谱的定性定量分析在其质量控制中的应用研究[J].安徽医药,待发表. |
| 重组全人抗PD-L1单克隆抗体N糖谱的定性定量分析在其质量控制中的应用研究 |
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| 投稿时间：2024-03-06 录用日期：2024-04-16 |
| DOI： |
| 中文关键词: 重组全人抗PD-L1单克隆抗体 N糖谱 超高效液相色谱-飞行时间高分辨质谱 定性和定量 |
| 英文关键词: |
| 基金项目:安徽省药品监督管理局2022年度药品监管科学研究重点项目(编号：AHYJ-KJ-202205) |
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| 中文摘要: |
| 目的 采用超高效液相色谱-飞行时间高分辨质谱联用技术，对重组全人抗PD-L1单克隆抗体的N糖谱进行定性和定量分析。方法 取11批次重组全人抗PD-L1单克隆抗体，其中正常批次3批、6个月加速试验正向和倒向放置分别3批，36个月长期试验正向和倒向放置分别1批。采用2-AB标记法，通过高分辨质谱对样品的N糖类型进行定性分析，通过荧光检测器对N糖含量进行定量检测。结果 通过高分辨质谱、葡聚糖标准品以及UNIFI数据库比对，各批次样品中共鉴定出10种N糖类型，主要是F(6)A1、A2、F(6)A2、M5等。10种N糖的色谱峰，峰形良好且完全分离，F(6)A2的含量在11批次样本中均约为91%，为最主要糖型。在6个月加速试验和36个月长期试验的样品中，正向和倒向放置样品，F(6)A2糖型也均达90%以上，糖型差异小，表明胶塞对全人抗PD-L1单克隆抗体无吸附作用。结论 重组全人抗PD-L1单克隆抗体的N糖型主要为F(6)A2，药品的生产工艺质量和药品稳定性良好，且重组全人抗PD-L1单克隆抗体和胶塞具有良好的相容性。 |
| 英文摘要: |
| Abstract Objective The N-glucose profiles for recombinant anti-human Programmed Cell Death Ligand 1 (PD-L1) monoclonal antibody was qualitatively and quantitatively analyzed by ultra-high performance liquid chromatography-time-of-flight high resolution mass spectrometry (UPLC-TOF HRMS) technique. Methods 11 batches of recombinant anti-human PD-L1 monoclonal antibody were obtained, including 3 batches of normal batches, 3 batches (upright and inversed) of 6-month accelerated test, 1 batches (upright and inversed) of 36-month long-term test. The N-glucose profiles were qualitatively analyzed by HRMS, and quantification for N-glucose was carried out on a fluorescence detector combined with the 2-AB labeling method. Results Combined with 2-AB dextran calibration ladder and UNIFI databases, 10 kinds of N-glucose types were identified through UPLC-TOF HRMS analysis, the typical N-glucose types were F(6)A1, A2, F(6)A2, and M5. The chromatographic peaks of N-glucoses were completely separated and get good peak shape, the F(6)A2 was the most abundant type of N-glucose and the content was approximately reach to 91% in all batch of samples. The results of 6-month accelerated test and 36-month long-term test show that the content of F(6)A2 was about equal to 91% in analyzed samples and there was no difference between the content of the N-glucose, indicating that the rubber stopper had no absorption effect on the recombinant anti-human PD-L1 monoclonal antibody. Conclusion The F(6)A2 was the most abundant of the N-glucose type in the recombinant anti-human PD-L1 monoclonal antibody, the production process and the drug stability were relatively stable, and the recombinant anti-human PD-L1 monoclonal antibody had good compatibility with the rubber stopper. |
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