Simultaneous Quantification of Total Antibody and Conjugated Payload for DS001 in Rat Serum Using a Hybrid Immuno-Capture LC-MS/MS
文献类型：期刊论文
| 作者 | Yu, Xiong3,4; Li, Weiqiang2,3; Huang, Wensi2,3; Xiao, Bo3,4; Long, Jing3; Wang, Qi3; Wang, Guifeng3 ; Wang, Chunhe3; Yu, Mingming1,4; Yu, Jinghua3
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| 刊名 | AAPS JOURNAL
 |
| 出版日期 | 2025-01-07 |
| 卷号 | 27期号:1页码:13 |
| 关键词 | ADC LC-MS/MS payload simultaneous quantification total antibody |
| ISSN号 | 1550-7416 |
| DOI | 10.1208/s12248-024-01007-4 |
| 通讯作者 | Yu, Mingming(yumingming@ouc.edu.cn) ; Yu, Jinghua(yujinghua2@simm.ac.cn) ; Diao, Xingxing(xxdiao@simm.ac.cn) |
| 英文摘要 | Antibody-drug conjugates (ADCs) are intricate compounds that pose significant challenges in bioanalytical characterization. Therefore, multiple bioanalytical methods are required to comprehensively elucidate their pharmacokinetic (PK) profiles. In this study, we investigated DS001, an ADC consisting of a humanized monoclonal antibody (hRS7), a cleavable chemical linker, and the microtubule inhibitor monomethyl auristatin E (MMAE), with a drug-to-antibody ratio (DAR) of 8. This study established a rapid and sensitive hybrid immunoaffinity liquid-chromatography-tandem-mass-spectrometry (LC-MS/MS) approach for the simultaneous quantification of the total antibody and the enzymatically cleavable conjugated payload of DS001. This method is capable of monitoring fluctuations in average DAR values during PK assessments. The sample preparation procedure involved immunocapture, denaturation, trypsin digestion, papain digestion, and termination, all completed within a total processing time of less than 4 h. The method demonstrated linearity for the total antibody in the range of 100 ng/mL (lower-limit-of-quantification, LLOQ) to 100,000 ng/mL, and for the conjugated payload from 3.495 ng/mL (LLOQ) to 3495 ng/mL in rat serum. Both analytes exhibited standard curve correlation coefficients (r) greater than 0.990 within their respective linear ranges. The precision and accuracy of the method were within +/- 15% (+/- 20% for LLOQ). The verified LC-MS/MS approach was successfully employed in the PK analysis following intravenous administration of 0.2 mg/kg DS001 in rats via tail vein injection. |
| WOS关键词 | BIOANALYTICAL ASSAYS ; DRUG ; PHARMACOKINETICS ; VALIDATION ; STRATEGIES |
| 资助项目 | National Natural Science Foundation of China[82373938] ; National Natural Science Foundation of China[82104275] ; National Natural Science Foundation of China[82104276] ; National Natural Science Foundation of China[82204585] ; Key Technologies R&D Program of Guangdong Province[2023B1111030004] ; National Key R&D Program of China[2022YFF1202600] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001391660200002 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315612]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Yu, Mingming; Yu, Jinghua; Diao, Xingxing |
| 作者单位 | 1.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Drugs & Bioprod, Qingdao 266003, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201210, Peoples R China 4.Ocean Univ China, Sch Med & Pharm, Qingdao 266003, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yu, Xiong,Li, Weiqiang,Huang, Wensi,et al. Simultaneous Quantification of Total Antibody and Conjugated Payload for DS001 in Rat Serum Using a Hybrid Immuno-Capture LC-MS/MS[J]. AAPS JOURNAL,2025,27(1):13. |
| APA | Yu, Xiong.,Li, Weiqiang.,Huang, Wensi.,Xiao, Bo.,Long, Jing.,...&Diao, Xingxing.(2025).Simultaneous Quantification of Total Antibody and Conjugated Payload for DS001 in Rat Serum Using a Hybrid Immuno-Capture LC-MS/MS.AAPS JOURNAL,27(1),13. |
| MLA | Yu, Xiong,et al."Simultaneous Quantification of Total Antibody and Conjugated Payload for DS001 in Rat Serum Using a Hybrid Immuno-Capture LC-MS/MS".AAPS JOURNAL 27.1(2025):13. |
入库方式： OAI收割
来源：上海药物研究所
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