Liquid chromatography-mass spectrometry method for the quantification of an anti-sclerostin monoclonal antibody in cynomolgus monkey serum

doi:10.1016/j.jpha.2020.08.005

	Liquid chromatography-mass spectrometry method for the quantification of an anti-sclerostin monoclonal antibody in cynomolgus monkey serum
	Gao, Yuxiong 1,2; Chen, Zhendong 1,2; Yang, Changyong 3; Zhong, Dafang 1,2
刊名	JOURNAL OF PHARMACEUTICAL ANALYSIS
	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.
资助项目	National Natural Science Foundation of China[81521005] ; National Key Research Project of the Chinese Academy of Sciences[XDA12050306]
WOS关键词	RISK-BASED APPROACH ; THERAPEUTIC ANTIBODIES ; LC-MS/MS ; IMMUNOGENICITY ; PRODUCTS ; PROTEIN ; RECOMMENDATIONS ; QUANTITATION ; COMPLEXES ; STRATEGY
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER
WOS记录号	WOS:000691800500009
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297744]
专题	中国科学院上海药物研究所
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.