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

Chunling Zhou; Xiaoxin Li; Aiping He; Tianzhu Liu; Jinmiao Tian; Meihua Jiang; Lina Fang

doi:10.1155/2020/8811522

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

J Anal Methods Chem. 2020 Dec 16:2020:8811522. doi: 10.1155/2020/8811522. eCollection 2020.

Authors

Chunling Zhou¹, Xiaoxin Li¹, Aiping He¹, Tianzhu Liu¹, Jinmiao Tian¹, Meihua Jiang², Lina Fang²

Affiliations

¹ Liaoning Institute for Drug Control, Liaoning Inspection, Examination & Certification Centre, Shenyang 110035, China.
² College of Pharmacy, Shenyang Medical College, Shenyang 110034, China.

Abstract

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.