| 冯蕊,蔡娜,查萍萍,等.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,2026,30(1):78-82. |
| 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 |
| The qualitative and quantitative analysis of N-glycan profilesfor recombinant fully human anti-PD-L1 monoclonal antibody in its quality control |
| |
| DOI：10.3969/j.issn.1009-6469.2026.01.016 |
| 中文关键词: 抗体，单克隆 程序性死亡配体 1(PD-L1) N-聚糖 重组全人抗 PD-L1单克隆抗体 超高效液相色谱 -飞行时间高分辨质谱(UPLC-TOFHRMS) 稳定性加速试验 质量控制 |
| 英文关键词: Antibodies,monoclonal Programmed death-ligand 1 (PD-L1) N-glycan Recombinant fully human anti-PD-L1 mono-clonal antibody Ultra-high performance liquid chromatography-time-of-flight high resolution mass spectrometry (UPLC-TOF HRMS) Accelerated stability test Quality control |
| 基金项目:安徽省药品监督管理局药品监管科学研究重点项目( AHYJ-KJ-202205) |
| 作者 | 单位 | E-mail | | 冯蕊 | 安徽医科大学,药学科学学院,安徽合肥 230032
炎症免疫性疾病安徽省实验室,安徽合肥 230032 | | | 蔡娜 | 安徽医科大学,药学科学学院,安徽合肥 230032 | | | 查萍萍 | 池州市质量监督检验研究院,安徽池州 247099 | | | 汪生 | 安徽医科大学,科研实验中心,安徽合肥 230032 | | | 许雷鸣 | 安徽省食品药品检验研究院,安徽合肥 230051 | | | 马陶陶 | 安徽医科大学,药学科学学院,安徽合肥 230032
炎症免疫性疾病安徽省实验室,安徽合肥 230032 | mataotao@ahmu.edu.cn |
|
| 摘要点击次数: 410 |
| 全文下载次数: 941 |
| 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，对重组全人抗程序性死亡配体 -1(PD-L1)单克隆抗体的 N糖谱进行定性和定量分析。方法选取 2020年 3月至 2023年 3月共 11批次重组全人抗 PD-L1单克隆抗体［安徽省食品药品检验研究院生物制品(药理)室］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-氨基苯甲酰胺，(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: |
| Objective To qualitatively and quantitatively analyze the N-glycan profiles for recombinant fully human anti-Pro-grammed Cell Death Ligand 1 (PD-L1) monoclonal antibody by ultra-high performance liquid chromatography-time-of-flight high reso-lution mass spectrometry (UPLC-TOF HRMS) technique. Methods A total of 11 batches of recombinant fully human anti-PD-L1 monoclonal antibody produced from March 2020 to March 2023 were selected [The antibody was provided by the Biologics (Pharmacol-ogy) Department of Anhui Institute for Food and Drug Control], including 3 batches of normal batches, 3 respective batches (uprightand inversed) of 6-month accelerated test, 1 batch (upright and inversed) of 36-month long-term test. The N-glycan profiles were quali-tatively analyzed by HRMS using the 2-aminobenzamide (2-AB) labeling method, and quantification for N-glycan was carried out on a fluorescence detector.Results Combined with 2-AB dextran calibration ladder and UNIFI databases, 10 kinds of N-glycans were iden-tified through UPLC-TOF HRMS analysis, the typical N-glycan types were F(6)A1, A2, F(6)A2, and M5. The chromatographic peaks of N-glycans were completely separated and got good peak shape. The F(6)A2 glycan was the most abundant type of N-glycan in this anti-body. The samples (upright and inversed) of 6-month accelerated test and 36-month long-term test showed that the F(6)A2 glycan allreached over 90%, and there was no difference in glycans, indicating that the rubber stopper had no absorption effect on the recombi-nant fully human anti-PD-L1 monoclonal antibody.Conclusion F(6)A2 glycan is the predominant N-glycan in the recombinant fully human anti-PD-L1 monoclonal antibody, the production process and the drug stability are relatively stable, and the recombinant fully human anti-PD-L1 monoclonal antibody has good compatibility with the rubber stopper. |
|
查看全文
查看/发表评论 下载PDF阅读器 |
| 关闭 |
|
|
|
