Development and validation of bioanalytical methods to support clinical study of disitamab vedotin.

IF 1.9 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS

Bioanalysis Pub Date : 2024-01-01 Epub Date: 2024-03-26 DOI:10.4155/bio-2023-0230

Baiyang Wu, Qiaoning Li, Ling Wang, Fang Chen, Jing Jiang

引用次数: 0

Abstract

Disitamab vedotin (RC48), a humanized anti-HER2 antibody conjugated with monomethyl auristatin E (MMAE), is the first antibody-drug conjugate in China with an approved biological license application. A bioanalytical method was established for three analytes (total antibody, conjugate antibody and free payload) to help characterize their pharmacokinetic behavior in clinical settings. The bioanalytical methods were validated according to M10 guidance. Electrochemiluminescence assay methods were used for the quantitative measurement of total antibody and conjugated antibody in human serum. A LC-MS/MS method was used to quantify the concentration of MMAE in human serum. The method had high specificity and sensitivity with a quantitative range of 19.531-1250.000 ng/ml (total antibody), 39.063-5000.000 ng/ml (conjugated antibody) and 0.04-10.0 ng/ml (MMAE), respectively.

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开发和验证生物分析方法，以支持迪西他单抗维多汀的临床研究。

Disitamab vedotin（RC48）是一种与单甲基金刚烷E（MMAE）共轭的人源化抗HER2抗体，也是中国首个获得生物许可申请的抗体药物共轭物。该研究建立了三种分析物（总抗体、共轭抗体和游离有效载荷）的生物分析方法，以帮助描述它们在临床环境中的药代动力学行为。生物分析方法根据 M10 指南进行了验证。电化学发光检测法用于定量检测人血清中的总抗体和共轭抗体。LC-MS/MS 方法用于定量检测人体血清中 MMAE 的浓度。该方法的特异性和灵敏度较高，定量范围分别为 19.531-1250.000 ng/ml（总抗体）、39.063-5000.000 ng/ml（共轭抗体）和 0.04-10.0 ng/ml（MMAE）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioanalysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

3.30

自引率

16.70%

发文量

审稿时长

2 months

期刊介绍： Reliable data obtained from selective, sensitive and reproducible analysis of xenobiotics and biotics in biological samples is a fundamental and crucial part of every successful drug development program. The same principles can also apply to many other areas of research such as forensic science, toxicology and sports doping testing. The bioanalytical field incorporates sophisticated techniques linking sample preparation and advanced separations with MS and NMR detection systems, automation and robotics. Standards set by regulatory bodies regarding method development and validation increasingly define the boundaries between speed and quality. Bioanalysis is a progressive discipline for which the future holds many exciting opportunities to further reduce sample volumes, analysis cost and environmental impact, as well as to improve sensitivity, specificity, accuracy, efficiency, assay throughput, data quality, data handling and processing. The journal Bioanalysis focuses on the techniques and methods used for the detection or quantitative study of analytes in human or animal biological samples. Bioanalysis encourages the submission of articles describing forward-looking applications, including biosensors, microfluidics, miniaturized analytical devices, and new hyphenated and multi-dimensional techniques. Bioanalysis delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for the modern bioanalyst.