通过液相色谱-串联质谱法对自行车®毒素共轭物 BT5528 和释放的单甲基金丝桃素 E 进行生物分析。

IF 1.9 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS Bioanalysis Pub Date : 2024-02-01 Epub Date: 2023-12-13 DOI:10.4155/bio-2023-0189

Joseph A Tweed, Fern Adams-Dam, Jane Allanson, Kevin Holmes, Ryan Senior, Hongmei Xu, Mengyao Li, Gavin Bennett, Phil Jeffrey

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引用次数: 0

摘要

背景：Bicycle® 毒素共轭物 BT5528 是一种新型多肽疗法，与细胞毒剂单甲基乌司他丁 E（MMAE）共轭。我们开发了一种生物分析测定法来定量检测人体血浆中的 BT5528 和未结合的 MMAE。方法：BT5528 的定量采用蛋白质沉淀程序，然后进行 LC-MS/MS 检测。MMAE 的定量需要选择性离线和在线固相萃取，并通过 LC-MS/MS 进行检测。结果BT5528 的定量检测范围为 5-2500 纳克/毫升，游离 MMAE 的定量检测范围为 0.05-50 纳克/毫升。结论在一项 I/IIa 期临床试验中，采用生物分析方法对完整的 BT5528 和释放的 MMAE 进行了生物分析；迄今为止，已分析了 2000 多份人类患者样本。

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Bioanalysis of the Bicycle^® toxin conjugate BT5528 and released monomethyl auristatin E via liquid chromatography-tandem mass spectrometry.

Background: The Bicycle^® toxin conjugate BT5528 is a novel peptide therapeutic conjugated to the cytotoxic agent monomethyl auristatin E (MMAE). A bioanalytical assay was developed to quantify BT5528 and unconjugated MMAE in human plasma. Methodology: BT5528 quantitation used a protein precipitation procedure followed by LC-MS/MS detection. Quantitation of MMAE required a selective offline and online solid-phase extraction with detection via LC-MS/MS. Results: BT5528 was quantified over the assay range of 5-2500 ng/ml and free MMAE was quantified over the assay range of 0.05-50 ng/ml. Conclusion: Bioanalytical methods were used in the bioanalysis of intact BT5528 and released MMAE, in a phase I/IIa clinical trial; to date, over 2000 human patient samples have been analyzed.

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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.