开发和验证用于定量食蟹猴血浆中单甲基auristan E的超灵敏UPLC-MS/MS方法：应用于药代动力学研究
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.
摘要(中文译文)
抗体-药物偶联物（ADC）代表了癌症治疗中的前沿方法，其中单甲基澳瑞他汀E（MMAE）常被用作ADC开发中的载荷。我们建立了一种新型生物分析方法，该方法具有高灵敏度、准确性和高效性，可用于定量食蟹猴血浆中的MMAE。采用液-液萃取（LLE）提取MMAE，并通过液相色谱-串联质谱法（LC-MS/MS）进行定量。结果：该方法在食蟹猴血浆中5至3000 pg/mL的浓度范围内表现出良好的线性（≥0.99），并且符合精密度（CV≤15%，定量下限（LLOQ）为20%）和准确度（83.98-112.75%）标准，满足监管生物分析验证指南的验证要求。该经过验证的方法有助于探索ADC的体内药代动力学特征并阐明其暴露-效应动态关系。
Abstract
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. 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 ( ≥ 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. This validated method is instrumental in exploring the in vivo pharmacokinetic profile of ADC and elucidating their exposure-response dynamics.
如何引用
AMA
Bing Zhang, Lei Zhang, Yanfeng Liu, Weimin Hu, Rui Diao, Lili Xing, et al. 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.. Bioanalysis. 2026; doi:10.1080/17576180.2026.2641573.
APA
Bing Zhang, Lei Zhang, Yanfeng Liu, Weimin Hu, Rui Diao, Lili Xing, et al (2026). 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.. Bioanalysis. https://doi.org/10.1080/17576180.2026.2641573
GB/T 7714
Bing Zhang, Lei Zhang, Yanfeng Liu, Weimin Hu, Rui Diao, Lili Xing, et al. 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.[J]. Bioanalysis, 2026 doi:10.1080/17576180.2026.2641573.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出