Development and validation of an ultra-sensitive UPLC-MS/MS method for quantification of monomethyl auristatin E in cynomolgus monkey plasma: application to pharmacokinetic study.

IF 1.8 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS

Bioanalysis Pub Date : 2026-02-01 Epub Date: 2026-03-09 DOI:10.1080/17576180.2026.2641573

Bing Zhang, Lei Zhang, Yanfeng Liu, Weimin Hu, Rui Diao, Lili Xing, Yi Tao, Liang Shen

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引用次数: 0

Abstract

Introduction: Antibody-drug conjugates (ADCs) represent a cutting-edge approach in cancer therapy, with monomethyl auristatin E (MMAE) frequently used as a payload in ADC development. We have established a novel bioanalytical method characterized by high sensitivity, accuracy, and efficiency for quantifying MMAE in cynomolgus monkey plasma.

Methodology: MMAE was extracted using liquid-liquid extraction (LLE) and quantified by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Results: The method exhibited excellent linearity across a concentration range of 5 to 3000 pg/mL (r ≥ 0.99) in cynomolgus monkey plasma, it fulfilled precision (CV ≤ 15%, 20% for lower limit of quantification (LLOQ)) and accuracy (83.98-112.75%) criteria according to meeting validation requirements per regulatory bioanalytical validation guidelines.

Conclusion: This validated method is instrumental in exploring the in vivo pharmacokinetic profile of ADC and elucidating their exposure-response dynamics.

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超灵敏UPLC-MS/MS定量食蟹猴血浆中单甲基耳草素E方法的建立与验证：在药动学研究中的应用

抗体-药物偶联物（ADC）代表了癌症治疗的一种前沿方法，单甲基aurisatin E （MMAE）经常被用作ADC开发的有效载荷。建立了一种灵敏、准确、高效的食蟹猴血浆中MMAE的定量分析方法。方法：采用液液萃取法（LLE）提取MMAE，液相色谱-串联质谱法（LC-MS/MS）定量。结果：该方法在食蟹猴血浆5 ~ 3000 pg/mL （r≥0.99）的浓度范围内呈良好的线性关系，满足精密度（CV≤15%，定量下限（LLOQ）为20%）和准确度（83.98 ~ 112.75%）标准，符合生物分析规范性验证指南的验证要求。结论：该方法有助于探索ADC的体内药动学特征，阐明其暴露-反应动力学。

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.