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

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...

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Main Authors: Chunling Zhou, Xiaoxin Li, Aiping He, Tianzhu Liu, Jinmiao Tian, Meihua Jiang, Lina Fang
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Journal of Analytical Methods in Chemistry
Online Access:http://dx.doi.org/10.1155/2020/8811522
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author Chunling Zhou
Xiaoxin Li
Aiping He
Tianzhu Liu
Jinmiao Tian
Meihua Jiang
Lina Fang
author_facet Chunling Zhou
Xiaoxin Li
Aiping He
Tianzhu Liu
Jinmiao Tian
Meihua Jiang
Lina Fang
author_sort Chunling Zhou
collection DOAJ
description 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.
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institution Kabale University
issn 2090-8865
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publishDate 2020-01-01
publisher Wiley
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series Journal of Analytical Methods in Chemistry
spelling doaj-art-4744dec1897841fc8fcb5180e179322d2025-02-03T06:43:42ZengWileyJournal of Analytical Methods in Chemistry2090-88652090-88732020-01-01202010.1155/2020/88115228811522Development of a UPLC-MS/MS Method for the Quantification of VS-5584 and Its Application in Pharmacokinetic Studies in RatsChunling Zhou0Xiaoxin Li1Aiping He2Tianzhu Liu3Jinmiao Tian4Meihua Jiang5Lina Fang6Liaoning Institute for Drug Control, Liaoning Inspection, Examination & Certification Centre, Shenyang 110035, ChinaLiaoning Institute for Drug Control, Liaoning Inspection, Examination & Certification Centre, Shenyang 110035, ChinaLiaoning Institute for Drug Control, Liaoning Inspection, Examination & Certification Centre, Shenyang 110035, ChinaLiaoning Institute for Drug Control, Liaoning Inspection, Examination & Certification Centre, Shenyang 110035, ChinaLiaoning Institute for Drug Control, Liaoning Inspection, Examination & Certification Centre, Shenyang 110035, ChinaCollege of Pharmacy, Shenyang Medical College, Shenyang 110034, ChinaCollege of Pharmacy, Shenyang Medical College, Shenyang 110034, ChinaVS-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.http://dx.doi.org/10.1155/2020/8811522
spellingShingle Chunling Zhou
Xiaoxin Li
Aiping He
Tianzhu Liu
Jinmiao Tian
Meihua Jiang
Lina Fang
Development of a UPLC-MS/MS Method for the Quantification of VS-5584 and Its Application in Pharmacokinetic Studies in Rats
Journal of Analytical Methods in Chemistry
title Development of a UPLC-MS/MS Method for the Quantification of VS-5584 and Its Application in Pharmacokinetic Studies in Rats
title_full Development of a UPLC-MS/MS Method for the Quantification of VS-5584 and Its Application in Pharmacokinetic Studies in Rats
title_fullStr Development of a UPLC-MS/MS Method for the Quantification of VS-5584 and Its Application in Pharmacokinetic Studies in Rats
title_full_unstemmed Development of a UPLC-MS/MS Method for the Quantification of VS-5584 and Its Application in Pharmacokinetic Studies in Rats
title_short Development of a UPLC-MS/MS Method for the Quantification of VS-5584 and Its Application in Pharmacokinetic Studies in Rats
title_sort development of a uplc ms ms method for the quantification of vs 5584 and its application in pharmacokinetic studies in rats
url http://dx.doi.org/10.1155/2020/8811522
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