快速、简便的LC-MS/MS定量测定人、小鼠血浆和小鼠组织中抗微管抗癌剂ABT-751的方法的建立与验证

IF 1.8 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Aristeidis Lentzas, Anna Their, Jos H. Beijnen, Mark C. de Gooijer, Olaf van Tellingen
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引用次数: 0

摘要

建立了靶向微管的抗癌药物ABT-751的快速选择性液相色谱-串联质谱(LC-MS/MS)定量方法并进行了验证。样品制备包括用乙腈和甲酸(100:1,v/v)沉淀蛋白质,在最小的离子抑制下提供高效的ABT-751提取。bupalisib (BKM-120)作为内标。色谱分离采用Zorbax Extend C18色谱柱,在0.1% (v/v)甲酸水溶液中,以20% ~ 95%甲醇梯度洗脱,正离子模式下进行MS/MS检测。该检测方法适用于人血浆、小鼠血浆和各种小鼠组织,包括脑、肝、肺和肾匀浆。除小鼠肿瘤组织外,在各空白生物基质中制备校正剂,在5 ~ 10000 nM范围内进行二次回归拟合曲线。对于小鼠肿瘤组织,我们使用人血浆作为校准剂的替代基质。在所有基质的低、中、高浓度下,日间和日间测量的精密度和准确度均在可接受范围内。确定并解决了ABT-751在储存超过8个月的小鼠血浆和组织匀浆样品中的稳定性问题。在小鼠体内进行的初步药代动力学研究证明了该方法的适用性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Development and Validation of a Rapid and Simple LC-MS/MS Method for Quantification of the Anti-Microtubule, Anti-Cancer Agent ABT-751 in Human and Mouse Plasma and Mouse Tissues

A rapid and selective liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantifying ABT-751, an anticancer agent targeting microtubules. Sample preparation involved protein precipitation using acetonitrile and formic acid (100:1, v/v), providing efficient ABT-751 extraction with minimal ion suppression. Buparlisib (BKM-120) served as the internal standard. Chromatographic separation was achieved on a Zorbax Extend C18 column, with gradient elution from 20 to 95% methanol in 0.1% (v/v) formic acid in water, and MS/MS detection was performed in positive ionization mode. This assay was validated for human plasma, mouse plasma, and various mouse tissues, including brain, liver, lung, and kidney homogenates. Calibrants were prepared in each respective blank biological matrix, except for mouse tumor tissue, and curves were fitted by quadratic regression from 5 to 10,000 nM. For mouse tumor tissue we used human plasma as surrogate matrix for calibrants. Precision and accuracy for intra-day and inter-day measurements were within acceptable limits across low, medium, and high concentrations for all matrices. Stability concerns with ABT-751 in mouse plasma and tissue homogenate samples that were stored for more than 8 months were identified and addressed. A pilot pharmacokinetic study in mice demonstrated the applicability of this validated LC-MS/MS method.

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来源期刊
Biomedical Chromatography
Biomedical Chromatography 生物-分析化学
CiteScore
3.60
自引率
5.60%
发文量
268
审稿时长
2.3 months
期刊介绍: Biomedical Chromatography is devoted to the publication of original papers on the applications of chromatography and allied techniques in the biological and medical sciences. Research papers and review articles cover the methods and techniques relevant to the separation, identification and determination of substances in biochemistry, biotechnology, molecular biology, cell biology, clinical chemistry, pharmacology and related disciplines. These include the analysis of body fluids, cells and tissues, purification of biologically important compounds, pharmaco-kinetics and sequencing methods using HPLC, GC, HPLC-MS, TLC, paper chromatography, affinity chromatography, gel filtration, electrophoresis and related techniques.
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