LC-MS /MS法同时定量人血浆中双靶向1,5-二芳基-1,2,4-三唑磺胺(WA11-13

IF 1.7 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Fawzy A. Elbarbry, Bethany Hecker, Michael J. Espiritu, Ahmed E. Elsawi, Wagdy M. Eldehna
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引用次数: 0

摘要

我们最近设计并合成了新型双靶向抗癌药物1,5-二芳基-1,2,4-三唑系链磺胺。其中WA11-13表现出良好的碳酸酐酶和VEGFR-2抑制活性。本研究提出了一种有效的、灵敏的LC-MS /MS测定方法,用于定量人血浆中的这些化合物。这对今后的临床前研究和治疗药物监测具有重要意义。用乙腈沉淀蛋白质后,在Phenomenex Kinetex C18色谱柱上用二元梯度洗脱分离分析物和内标物(卡马西平)。流动相为0.1%甲酸水溶液-乙腈(95:5,v/v),流速为0.7 mL/min。总运行时间低于6分钟。检测使用API 3500三重四极质谱仪,电喷雾电离模式为正模式。定量依赖于多反应监测,灵敏度和特异性高。该方法根据FDA指南进行了充分验证,显示出可接受的线性、准确度、精密度、选择性和稳定性。WA11在2.5 ~ 750 ng/mL、WA12在25 ~ 1000 ng/mL、WA13在50 ~ 1000 ng/mL范围内呈线性关系。该方法已成功应用于加标人血浆,支持其治疗药物监测的潜力。验证证实了该检测方法的高灵敏度、准确性和精密度,使其适用于这些正在研究的抗癌药物的临床前和临床研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
LC–MS/MS Assay for Simultaneous Quantification of Dual-Targeting 1,5-Diaryl-1,2,4-Triazole Sulfonamides (WA11–13) in Human Plasma

We recently designed and synthesized novel dual-targeting anticancer 1,5-diaryl-1,2,4-triazole-tethered sulfonamides. Among them, WA11–13 showed promising carbonic anhydrase and VEGFR-2 inhibitory activity. This study presents a validated, sensitive LC–MS/MS assay for quantifying these compounds in human plasma. Such assay would be very important for future preclinical studies and therapeutic drug monitoring. After protein precipitation with acetonitrile, analytes and the internal standard (carbamazepine) were separated on a Phenomenex Kinetex C18 column using binary gradient elution. The mobile phase was 0.1% formic acid in water and acetonitrile (95:5, v/v) at 0.7 mL/min. Total run time was under 6 min. Detection used an API 3500 triple quadrupole mass spectrometer with electrospray ionization in positive mode. Quantification relied on multiple reaction monitoring for high sensitivity and specificity. The method was fully validated per FDA guidelines, showing acceptable linearity, accuracy, precision, selectivity, and stability. Linearity was observed in the ranges of 2.5–750 ng/mL for WA11, 25–1000 ng/mL for WA12, and 50–1000 ng/mL for WA13. The method was successfully applied to spiked human plasma, supporting its potential for therapeutic drug monitoring. Validation confirms the assay's high sensitivity, accuracy, and precision, making it suitable for future preclinical and clinical investigations of these investigational anticancer agents.

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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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