Characterization of Alpelisib in Rat Plasma by a Newly Developed UPLC-MS/MS Method: Application to a Drug-Drug Interaction Study

Alpelisib, an oral selective and small-molecule phosphoinositide 3-kinase inhibitor, was lately approved in the United States to treat breast cancer. A sensitive method to quantify alpelisib levels in rat plasma on the basis of ultra-performance liquid chromatography–tandem mass spectrometry techniq...

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Autores principales:	Qiong Wang, Xia Lan, Zhuofei Zhao, Xiaohang Su, Yuji Zhang, Xiao-Yang Zhou, Ren-Ai Xu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	drug interaction pharmacokinetics CYP3A4 inhibitors ultra-performance liquid chromatography–tandem mass spectrometry alpelisib Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/91ae63712cda4957bb5b949d3d971fe7
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spelling	oai:doaj.org-article:91ae63712cda4957bb5b949d3d971fe72021-12-01T01:27:35ZCharacterization of Alpelisib in Rat Plasma by a Newly Developed UPLC-MS/MS Method: Application to a Drug-Drug Interaction Study1663-981210.3389/fphar.2021.743411https://doaj.org/article/91ae63712cda4957bb5b949d3d971fe72021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.743411/fullhttps://doaj.org/toc/1663-9812Alpelisib, an oral selective and small-molecule phosphoinositide 3-kinase inhibitor, was lately approved in the United States to treat breast cancer. A sensitive method to quantify alpelisib levels in rat plasma on the basis of ultra-performance liquid chromatography–tandem mass spectrometry technique was established and validated, which was successfully employed to explore the effects of CYP3A4 inhibitors on alpelisib pharmacokinetics in rats. A C18 column named Acquity UPLC BEH C18 was applied to achieve the separation of alpelisib and internal standard duvelisib after protein precipitation with acetonitrile. The mobile phase in this study had two components, namely, acetonitrile and water having 0.1% formic acid, and a program with gradient elution method was used at a flow rate of 0.40 ml/min. Mass spectrometry in a positive multiple reaction monitoring mode was operated. In the scope of 1–5,000 ng/ml, this assay had excellent linearity. Our newly developed assay was verified in all aspects of bioanalytical method validation, involving lower limit of quantification, selectivity, accuracy and precision, calibration curve, extraction recovery, matrix effect, and stability. Then, this assay was used to detect the plasma levels of alpelisib from a drug-drug interaction investigation, where ketoconazole remarkably increased the plasma concentration of alpelisib and changed alpelisib pharmacokinetics more than itraconazole. This study will help better understand the pharmacokinetic properties of alpelisib, and further clinical studies should be done to confirm this result in patients.Qiong WangXia LanZhuofei ZhaoXiaohang SuYuji ZhangXiao-Yang ZhouRen-Ai XuFrontiers Media S.A.articledrug interactionpharmacokineticsCYP3A4 inhibitorsultra-performance liquid chromatography–tandem mass spectrometryalpelisibTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	drug interaction pharmacokinetics CYP3A4 inhibitors ultra-performance liquid chromatography–tandem mass spectrometry alpelisib Therapeutics. Pharmacology RM1-950
spellingShingle	drug interaction pharmacokinetics CYP3A4 inhibitors ultra-performance liquid chromatography–tandem mass spectrometry alpelisib Therapeutics. Pharmacology RM1-950 Qiong Wang Xia Lan Zhuofei Zhao Xiaohang Su Yuji Zhang Xiao-Yang Zhou Ren-Ai Xu Characterization of Alpelisib in Rat Plasma by a Newly Developed UPLC-MS/MS Method: Application to a Drug-Drug Interaction Study
description	Alpelisib, an oral selective and small-molecule phosphoinositide 3-kinase inhibitor, was lately approved in the United States to treat breast cancer. A sensitive method to quantify alpelisib levels in rat plasma on the basis of ultra-performance liquid chromatography–tandem mass spectrometry technique was established and validated, which was successfully employed to explore the effects of CYP3A4 inhibitors on alpelisib pharmacokinetics in rats. A C18 column named Acquity UPLC BEH C18 was applied to achieve the separation of alpelisib and internal standard duvelisib after protein precipitation with acetonitrile. The mobile phase in this study had two components, namely, acetonitrile and water having 0.1% formic acid, and a program with gradient elution method was used at a flow rate of 0.40 ml/min. Mass spectrometry in a positive multiple reaction monitoring mode was operated. In the scope of 1–5,000 ng/ml, this assay had excellent linearity. Our newly developed assay was verified in all aspects of bioanalytical method validation, involving lower limit of quantification, selectivity, accuracy and precision, calibration curve, extraction recovery, matrix effect, and stability. Then, this assay was used to detect the plasma levels of alpelisib from a drug-drug interaction investigation, where ketoconazole remarkably increased the plasma concentration of alpelisib and changed alpelisib pharmacokinetics more than itraconazole. This study will help better understand the pharmacokinetic properties of alpelisib, and further clinical studies should be done to confirm this result in patients.
format	article
author	Qiong Wang Xia Lan Zhuofei Zhao Xiaohang Su Yuji Zhang Xiao-Yang Zhou Ren-Ai Xu
author_facet	Qiong Wang Xia Lan Zhuofei Zhao Xiaohang Su Yuji Zhang Xiao-Yang Zhou Ren-Ai Xu
author_sort	Qiong Wang
title	Characterization of Alpelisib in Rat Plasma by a Newly Developed UPLC-MS/MS Method: Application to a Drug-Drug Interaction Study
title_short	Characterization of Alpelisib in Rat Plasma by a Newly Developed UPLC-MS/MS Method: Application to a Drug-Drug Interaction Study
title_full	Characterization of Alpelisib in Rat Plasma by a Newly Developed UPLC-MS/MS Method: Application to a Drug-Drug Interaction Study
title_fullStr	Characterization of Alpelisib in Rat Plasma by a Newly Developed UPLC-MS/MS Method: Application to a Drug-Drug Interaction Study
title_full_unstemmed	Characterization of Alpelisib in Rat Plasma by a Newly Developed UPLC-MS/MS Method: Application to a Drug-Drug Interaction Study
title_sort	characterization of alpelisib in rat plasma by a newly developed uplc-ms/ms method: application to a drug-drug interaction study
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/91ae63712cda4957bb5b949d3d971fe7
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Characterization of Alpelisib in Rat Plasma by a Newly Developed UPLC-MS/MS Method: Application to a Drug-Drug Interaction Study

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