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Development of a UPLC-MS/MS Method for the Quantification of VS-5584 and Its Application in Pharmacokinetic Studies in Rats

机译:用于定量VS-5584的UPLC-MS / MS方法的研制及其在大鼠药代动力学研究中的应用

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VS-5584 is a small-molecular compound that showed equivalent activity against mTOR and all class I PI3K isoforms and demonstrated preclinical activity in diverse cancer cell lines and xenograft tumor model, and rational combination of VS-5584 and other target therapies achieved promising outcomes in oncology. In the present study, we established and validated a simple and sensitive UPLC-MS/MS method for the determination of VS-5584 in plasma samples. VS-5584 was separated via an Acquity UPLC BEH C18 column, with a mobile phase composed of acetonitrile and 0.2% formic acid in water (40?:?60). The calibration curve displayed a good linearity in the range of 1.0–1000?ng/mL, with satisfactory accuracy (?13.6%?
机译:VS-5584是一种小分子化合物,其表现出对MTOR和所有类I类PI3K同种型的相同活性,并在不同癌细胞系和异种移植肿瘤模型中表现出临床前活性,并且VS-5584和其他目标疗法的合理组合取得了有希望的结果肿瘤学。在本研究中,我们建立并验证了一种简单敏感的UPLC-MS / MS方法,用于测定等离子体样品中的VS-5584。通过ACCATE UPLC BEP C18柱分离VS-5584,其中由乙腈和0.2%甲酸组成的流动阶段在水中(40?:20)。校准曲线在1.0-1000的范围内显示出良好的线性度,精度令人满意(?13.6%?<ΔRe%?<8.8%)和精度(CV%,小于9.2%)。然后将验证的方法应用于大鼠的药代动力学研究。在给予10×mg / kg后,VS-5584被快速吸收并达到20μm≤72.0≤ng/ ml的峰值浓度并达到473.2℃±72.0℃。所建立的方法允许详细定量大鼠等离子体中的VS-5584,并可用来成功描述VS-5584的药代动力学分布。

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