Ligand-binding assays validated for quantitative bioanalysis of a novel antibody-drug conjugate in monkey serum and related application in a nonclinical study
文献类型：期刊论文
| 作者 | Hou, Yingying6; Miao, Jie6; Sun, Yajun5; Shi, Lili5; Lu, Ouyang1,6; Chen, Xiaoqiang6; Li, Ziyi6; Liu, Tingting6; Qin, Gang5; Qin, Qiuping4,6
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| 刊名 | JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
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| 出版日期 | 2025-02-01 |
| 卷号 | 131页码:11 |
| 关键词 | ADC LBA Validation GLP PK |
| ISSN号 | 1056-8719 |
| DOI | 10.1016/j.vascn.2024.107580 |
| 英文摘要 | Background: Antibody-drug conjugates (ADCs) are an emerging class of targeted therapeutics and are receiving growing attention in the pharmaceutical field. Here we aimed to validate two ligand binding assays for the quantitation of GQ1001, an ADC made of Trastuzumab site-specifically conjugated with DM1, in cynomolgus monkey serum, and then apply the validated assays to a nonclinical study. Methods: The quantitative methods for conjugated GQ1001 and total GQ1001 were validated against regulatory guidance documents on bioanalytical method validation under a Good Laboratory Practice (GLP)-compliant environment. The validated assays were applied to a single-dose pharmacokinetic (PK) study of GQ1001 conducted in cynomolgus monkeys. Results: Both intra- and inter-assay precision and accuracy met the priori-defined acceptance criteria. Neither matrix effect nor hemolysis effect were observed, and the impact of specific interferents on the assays was evaluated. Dilution linearity was good with the expected dilution factors and no hook effect till up to 20.2 mg/ mL of GQ1001 was noted. Besides, the stability of the ADC in monkey serum was found to be sufficient to cover the time required for sample storage and analysis. Furthermore, the assays demonstrated good parallelism determined with a study sample and good reproducibility acquired by incurred sample reanalysis (ISR). Using the validated assays, we obtained serum concentrations for the conjugated GQ1001 and the total GQ1001 in the single-dose PK study, and thereafter, evaluated their exposures over the dosing period. Conclusions: All tested performance parameters of the assays met the validation acceptance criteria, which supported the application of the two assays in the nonclinical PK study and allowed the evaluation of the related PK parameters for GQ1001. |
| WOS研究方向 | Pharmacology & Pharmacy ; Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:001399070000001 |
| 出版者 | ELSEVIER SCIENCE INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315884]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Liu, Tingting; Qin, Gang; Qin, Qiuping; Gong, Likun |
| 作者单位 | 1.Anling Biomed Suzhou Co Ltd, Suzhou, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Zhongshan Inst Drug Discovery, Zhongshan 528400, Peoples R China 3.Univ Chinese Acad Sci, Beijing 101408, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.GeneQuantum Healthcare Suzhou Co Ltd, Suzhou 215000, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, Dept Immunoassay & Immunochemistry, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hou, Yingying,Miao, Jie,Sun, Yajun,et al. Ligand-binding assays validated for quantitative bioanalysis of a novel antibody-drug conjugate in monkey serum and related application in a nonclinical study[J]. JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS,2025,131:11. |
| APA | Hou, Yingying.,Miao, Jie.,Sun, Yajun.,Shi, Lili.,Lu, Ouyang.,...&Gong, Likun.(2025).Ligand-binding assays validated for quantitative bioanalysis of a novel antibody-drug conjugate in monkey serum and related application in a nonclinical study.JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS,131,11. |
| MLA | Hou, Yingying,et al."Ligand-binding assays validated for quantitative bioanalysis of a novel antibody-drug conjugate in monkey serum and related application in a nonclinical study".JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS 131(2025):11. |
入库方式： OAI收割
来源：上海药物研究所
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