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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Format: | Article |
Language: | English |
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Wiley
2020-01-01
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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. |
format | Article |
id | doaj-art-4744dec1897841fc8fcb5180e179322d |
institution | Kabale University |
issn | 2090-8865 2090-8873 |
language | English |
publishDate | 2020-01-01 |
publisher | Wiley |
record_format | Article |
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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