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% < RE% < 8.8%) and precision (CV%, less than 9.2%). The validated method was then applied to a pharmacokinetic study in rats. After administration of 10 mg/kg, VS-5584 was absorbed quickly and reached a peak concentration of 473.2 ± 72.0 ng/mL after 20 min. The established method allows for the quantification of VS-5584 in rat plasma in detail and can be utilized to successfully describe the pharmacokinetic profile of VS-5584.

中文翻译：

---

VS-5584定量UPLC-MS / MS方法的建立及其在大鼠药代动力学研究中的应用

VS-5584是一种小分子化合物，对mTOR和所有I类PI3K亚型均具有同等活性，并且在多种癌细胞系和异种移植肿瘤模型中均表现出临床前活性，并且VS-5584与其他目标疗法的合理组合在ACS中取得了可喜的成果。肿瘤学。在本研究中，我们建立并验证了用于测定血浆样品中VS-5584的简单而灵敏的UPLC-MS / MS方法。VS-5584通过Acquity UPLC BEH C18色谱柱分离，流动相由乙腈和0.2％甲酸的水溶液（40:60）组成。校准曲线在1.0–1000 ng / mL的范围内显示出良好的线性，具有令人满意的精度（−13.6％<RE％<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。给药10 mg / kg后，VS-5584快速吸收，并在20分钟后达到473.2±72.0 ng / mL的峰值浓度。所建立的方法可对大鼠血浆中的VS-5584进行详细定量，并可用于成功描述VS-5584的药代动力学特征。