Two validated liquid chromatography-mass spectrometry methods with different pretreatments for the quantification of an anti-CD47 monoclonal antibody in rat and cynomolgus monkey serum compared with an electrochemiluminescence method

doi:10.1016/j.jpba.2019.112792

	Two validated liquid chromatography-mass spectrometry methods with different pretreatments for the quantification of an anti-CD47 monoclonal antibody in rat and cynomolgus monkey serum compared with an electrochemiluminescence method
	Gao, Yuxiong 1,2; Zhang, Dan 1; Yang, Changyong 3; Duan, Xiaotao 4; Li, Xiuli 1; Zhong, Dafang 1
刊名	JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
	2019-10-25
卷号	175 页码:11
关键词	Anti-CD47 monoclonal antibody LC-MS Adsorption issue Electrochemiluminescence Pharmacokinetics Cross-validation
ISSN号	0731-7085
DOI	10.1016/j.jpba.2019.112792
通讯作者	Li, Xiuli(xli@simm.ac.cn) ; Zhong, Dafang(dfzhong@simm.ac.cn)
英文摘要	Establishing reliable bioanalytical methods is essential to support pharmacokinetic (PK) studies in the preclinical and clinical evaluation of monoclonal antibody (mAb) drugs. Ligand binding assay (LBA) has always been the gold standard for protein quantification, whereas LC-MS has gradually become a promising alternative method for the study of pharmacokinetics of biotherapeutics with its advantages of accuracy and rapid method development. Here, we described for the first time two liquid chromatography-mass spectrometry (LC-MS) methods with different purification pretreatments, protein precipitation and immune affinity (IA) enrichment, along with one electrochemiluminescence (ECL) method for the quantification of an anti-CD47 monoclonal antibody (SHR-1603) in rat and cynomolgus monkey serum. An anti-adsorption reagent was added and digestion conditions were optimized to resolve the absorption issue of hydrophobic peptide in this study. These methods were all validated according to China Food and Drug Administration (CFDA) and European Medicines Agency (EMA) guidelines and were successfully applied to a preclinical study for the quantification of SHR-1603. The respective quantitative ranges of the three methods are respectively 250-500,000 ng/mL (protein precipitation), 100-100,000 ng/mL (IA) and 19.5-10,000 ng/mL (ECL). The two LC-MS methods were compared with ECL method respectively by the cross-validation using the Passing-Bablok regression and Bland-Altman plots. Systematic differences and proportional bias were observed between two LC-MS methods on the one hand and with the ECL method on the other hand. The drug concentrations obtained by the three methods showed good agreement in the low-dose group (ratios of drug exposure, 1.05-1.11), whereas the drug concentrations measured using the LC-MS methods were higher than those obtained by the ECL method in medium-dose and high-dose groups, which can be attributed to the forms of antibodies being determined (free and total). In conclusion, the established LC-MS methods exhibited superior accuracy, efficiency and cost-effectiveness for the PK assessment of SHR-1603 in the preclinical study. Thus, it provides a promising alternative to LBA in pre-clinical and clinical evaluation studies of mAb drugs in various matrices to facilitate the development of anti-tumor drugs. (C) 2019 Elsevier B.V. All rights reserved.
资助项目	National Natural Science Foundation of China[81521005] ; National Natural Science Foundation of China[81673387] ; National Key Research Project of the Chinese Academy of Sciences[XDA12050306]
WOS关键词	PLASMA ; PROTEIN ; IMMUNOGENICITY ; DIGESTION ; PRODUCTS ; STRATEGY
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER
WOS记录号	WOS:000485206900012
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/288801]
专题	中国科学院上海药物研究所
通讯作者	Li, Xiuli; Zhong, Dafang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201210, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.Hengrui Med Co Ltd, Preclin Dept, Lianyungang 222047, Jiangsu, Peoples R China 4.Beijing Inst Pharmacol & Toxicol, State Key Lab Toxicol & Med Countermeasures, Beijing 100850, Peoples R China
推荐引用方式 GB/T 7714	Gao, Yuxiong,Zhang, Dan,Yang, Changyong,et al. Two validated liquid chromatography-mass spectrometry methods with different pretreatments for the quantification of an anti-CD47 monoclonal antibody in rat and cynomolgus monkey serum compared with an electrochemiluminescence method[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2019,175:11.
APA	Gao, Yuxiong,Zhang, Dan,Yang, Changyong,Duan, Xiaotao,Li, Xiuli,&Zhong, Dafang.(2019).Two validated liquid chromatography-mass spectrometry methods with different pretreatments for the quantification of an anti-CD47 monoclonal antibody in rat and cynomolgus monkey serum compared with an electrochemiluminescence method.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,175,11.
MLA	Gao, Yuxiong,et al."Two validated liquid chromatography-mass spectrometry methods with different pretreatments for the quantification of an anti-CD47 monoclonal antibody in rat and cynomolgus monkey serum compared with an electrochemiluminescence method".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 175(2019):11.