Liquid chromatography-mass spectrometry method for the quantification of an anti-sclerostin monoclonal antibody in cynomolgus monkey serum
文献类型：期刊论文
| 作者 | Gao, Yuxiong1,2; Chen, Zhendong1,2; Yang, Changyong3; Zhong, Dafang1,2
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| 刊名 | JOURNAL OF PHARMACEUTICAL ANALYSIS
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| 出版日期 | 2021-08-01 |
| 卷号 | 11期号:4页码:472-479 |
| 关键词 | Anti-sclerostin monoclonal antibody (SHR-1222) LC-MS/MS Anti-drug antibody Toxicokinetic |
| ISSN号 | 2095-1779 |
| DOI | 10.1016/j.jpha.2020.08.005 |
| 通讯作者 | Zhong, Dafang(dfzhong@simm.ac.cn) |
| 英文摘要 | Liquid chromatography tandem mass spectrometry (LC-MS/MS) has gradually become a promising alternative to ligand binding assay for the bioanalysis of biotherapeutic molecules, due to its rapid method development and high accuracy. In this study, we established a new LC-MS/MS method for the determination of the anti-sclerostin monoclonal antibody (SHR-1222) in cynomolgus monkey serum, and compared it to a previous electrochemiluminescence method. The antibody was quantified by detecting the surrogate peptide obtained by trypsin digestion. The surrogate peptide was carefully selected by investigating its uniqueness, stability and MS response. The quantitative range of the proposed method was 2.00-500 ttg/mL, and this verified method was successfully applied to the toxicokinetic assessment of SHR-1222 in cynomolgus monkey serum. It was found that the concentrations of SHR-1222 in cynomolgus monkeys displayed an excellent agreement between the LC-MS/MS and electrochemiluminescence methods (ratios of drug exposure, 0.8-1.0). Notably, two monkeys in the 60 mg/kg dose group had abnormal profiles with a low detection value of SHR-1222 in their individual sample. Combining the high-level anti-drug antibodies (ADAs) in these samples and the consistent quantitative results of the two methods, we found that the decreased concentration of SHR-1222 was due to the accelerated clearance mediated by ADAs rather than the interference of ADAs to the detection platform. Taken together, we successfully developed an accurate, efficient and cost-effective LC-MS/MS method for the quantification of SHR-1222 in serum samples, which could serve as a powerful tool to improve the preclinical development of antibody drugs. (C) 2020 Xi'an Jiaotong University. Production and hosting by Elsevier B.V. |
| WOS关键词 | RISK-BASED APPROACH ; THERAPEUTIC ANTIBODIES ; LC-MS/MS ; IMMUNOGENICITY ; PRODUCTS ; PROTEIN ; RECOMMENDATIONS ; QUANTITATION ; COMPLEXES ; STRATEGY |
| 资助项目 | National Natural Science Foundation of China[81521005] ; National Key Research Project of the Chinese Academy of Sciences[XDA12050306] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000691800500009 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/297744]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhong, Dafang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201210, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Hengrui Med Co Ltd, Preclin Dept, Lianyungang 222047, Jiangsu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gao, Yuxiong,Chen, Zhendong,Yang, Changyong,et al. Liquid chromatography-mass spectrometry method for the quantification of an anti-sclerostin monoclonal antibody in cynomolgus monkey serum[J]. JOURNAL OF PHARMACEUTICAL ANALYSIS,2021,11(4):472-479. |
| APA | Gao, Yuxiong,Chen, Zhendong,Yang, Changyong,&Zhong, Dafang.(2021).Liquid chromatography-mass spectrometry method for the quantification of an anti-sclerostin monoclonal antibody in cynomolgus monkey serum.JOURNAL OF PHARMACEUTICAL ANALYSIS,11(4),472-479. |
| MLA | Gao, Yuxiong,et al."Liquid chromatography-mass spectrometry method for the quantification of an anti-sclerostin monoclonal antibody in cynomolgus monkey serum".JOURNAL OF PHARMACEUTICAL ANALYSIS 11.4(2021):472-479. |
入库方式： OAI收割
来源：上海药物研究所
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