干旱区生态环境知识资源中心(Arid): Development and validation of an LC-MS/MS method to quantify the bromodomain and extra-terminal (BET) inhibitor JQ1 in mouse plasma and brain microdialysate: Application to cerebral microdialysis study

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DOI	10.1016/j.jpba.2021.114274
	Development and validation of an LC-MS/MS method to quantify the bromodomain and extra-terminal (BET) inhibitor JQ1 in mouse plasma and brain microdialysate: Application to cerebral microdialysis study
	Nair, Sreenath; Davis, Abigail; Campagne, Olivia; Schuetz, John D.; Stewart, Clinton F.
通讯作者	Stewart, CF (corresponding author), St Jude Childrens Res Hosp, Dept Pharmaceut Sci, 262 Danny Thomas Pl, Memphis, TN 38105 USA.
来源期刊	JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
ISSN	0731-7085
EISSN	1873-264X
出版年	2021
卷号	204
英文摘要	JQ1, is a cell-permeable small-molecule inhibitor of bromodomain and extra-terminal protein (BET) function with reportedly good CNS penetration, however, unbound and pharmacologically active CNS JQ1 exposures have not been characterized. Additionally, no quantitative bioanalytical methods for JQ1 have been described in the literature to support the CNS penetration studies. In the present article, we discuss the development and validation of a sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantitative methods to determine JQ1 in mouse plasma and brain microdialysate. JQ1 and the internal standard, dabrafenib (ISTD), were extracted from plasma and microdialysate samples using a simple solid phase extraction protocol performed on an Oasis HLB mu Elution plate. Chromatographic separation of JQ1 and ISTD was achieved on a reversed phase C-12 analytical column with gradient elution profile of mobile phases (MP A: water containing 0.1 % formic acid and MP B: acetonitrile containing 0.1 % formic acid) at a flow rate of 0.6 mL/min. The mass spectrometric detection was performed in the positive MRM ion mode by monitoring the transitions 457.40 > 341.30 (JQ1) and 520.40 > 307.20 (ISTD). The calibration curves demonstrated good linearities over the concentration range of 5-1000 ng/mL for the mouse plasma method (r(2) >= 0.99) and 0.5-500 ng/mL for the microdialysate method (r(2) >= 0.99). The experimental limit of quantification obtained was 5 and 0.5 ng/mL for the mouse plasma and microdialysate method, respectively, with the coefficient of variation less than 10 % for the analyte peak area. All the other validation parameters, including intra-and inter-day accuracy and precision, matrix effect, selectivity, carryover effect, and stability, were within the USFDA bioanalytical guidelines acceptance limits. The LC-MS/MS method was successfully applied to a mouse pharmacokinetic and cerebral microdialysis study to characterize the unbound JQ1 exposure in brain extracellular fluid and plasma. (C) 2021 Elsevier B.V. All rights reserved.
英文关键词	JQ1 BET inhibitor LC-MS/MS Solid phase extraction Pharmacokinetics Cerebral microdialysis
类型	Article
语种	英语
收录类别	SCI-E
WOS记录号	WOS:000686903700018
WOS类目	Chemistry, Analytical ; Pharmacology & Pharmacy
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/363986
作者单位	[Nair, Sreenath; Davis, Abigail; Campagne, Olivia; Schuetz, John D.; Stewart, Clinton F.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, 262 Danny Thomas Pl, Memphis, TN 38105 USA
推荐引用方式 GB/T 7714	Nair, Sreenath,Davis, Abigail,Campagne, Olivia,et al. Development and validation of an LC-MS/MS method to quantify the bromodomain and extra-terminal (BET) inhibitor JQ1 in mouse plasma and brain microdialysate: Application to cerebral microdialysis study[J],2021,204.
APA	Nair, Sreenath,Davis, Abigail,Campagne, Olivia,Schuetz, John D.,&Stewart, Clinton F..(2021).Development and validation of an LC-MS/MS method to quantify the bromodomain and extra-terminal (BET) inhibitor JQ1 in mouse plasma and brain microdialysate: Application to cerebral microdialysis study.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,204.
MLA	Nair, Sreenath,et al."Development and validation of an LC-MS/MS method to quantify the bromodomain and extra-terminal (BET) inhibitor JQ1 in mouse plasma and brain microdialysate: Application to cerebral microdialysis study".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 204(2021).