Simultaneous quantitation of 3-n-butylphthalide (NBP) and its four major metabolites in human plasma by LC-MS/MS using deuterated internal standards

doi:10.1016/j.jpba.2013.01.033

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	Simultaneous quantitation of 3-n-butylphthalide (NBP) and its four major metabolites in human plasma by LC-MS/MS using deuterated internal standards
	Diao, Xingxing 1; Ma, Zhiyu 1; Wang, Haidong 3; Zhong, Dafang1,2,3 ; Zhang, Yifan1 ; Jin, Jing 2; Fan, Yaxin 3; Chen, Xiaoyan1
刊名	JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
	2013-05-05
卷号	78-79 页码:19-26
关键词	3-n-Butylphthalide (NBP) Deuterated internal standard LC-MS/MS Pharmacokinetics Negative-positive ionization switching
ISSN号	0731-7085
DOI	10.1016/j.jpba.2013.01.033
文献子类	Article
英文摘要	3-n-Butylphthalide (NBP) is a cardiovascular drug widely used in China for the treatment of cerebral ischemic stroke. Our previous study showed that NBP underwent extensive metabolism in humans and that 10-keto-NBP (M2), 3-hydroxy-NBP (M3-1), 10-hydroxy-NBP (M3-2) and NBP-11-oic acid (M5-2) were the major circulating metabolites. A better understanding of the plasma exposures of NBP and its four major metabolites is crucial to supporting the safety evaluation, good clinic practice and discovery of new antistroke drugs. Herein, a liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of NBP, M2, M3-1, M3-2, and M5-2 in human plasma. To improve assay sensitivity and achieve simultaneous analysis, M3-1 and M5-2 were monitored in (-)ESI (electrospray) mode within the first 3.5 min and NBP, M2, and M3-2 thereafter in (+)ESI mode. Deuterated internal standards for all analytes were synthesized to compensate for the impact of matrix effects. Based on the vast differences in physicochemical properties among the five analytes and the necessary baseline separation of two isomers (i.e., M3-1 and M3-2), gradient elution comprising a mobile phase of methanol-acetonitrile-5 mM ammonium acetate was used after methanol-induced protein precipitation of plasma samples. The developed method was linear in the concentration range of 3.00-800 ng/ml for NBP and M2, and 3.00-2400 ng/ml for M3-1, M3-2, and M5-2. The lower limit of quantitation was 3.00 ng/ml for each analyte. The intra- and inter-day accuracy and precision were within acceptable limits (+/- 15%) at all concentrations. The method was successfully applied to characterize the pharmacokinetic profiles of NBP and its major metabolites following a single oral administration of 200 mg NBP to healthy volunteers. (C) 2013 Elsevier B.V. All rights reserved.
WOS关键词	TANDEM MASS-SPECTROMETRY ; CEREBRAL-BLOOD-FLOW ; LIQUID-CHROMATOGRAPHY ; RAT PLASMA ; DL-3-N-BUTYLPHTHALIDE ; QUANTIFICATION ; IDENTIFICATION ; VALIDATION ; EXTRACTION ; MODEL
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000317442800004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277621]
专题	上海药物代谢研究中心
通讯作者	Chen, Xiaoyan
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Soochow Univ, Coll Pharm, Suzhou 215123, Peoples R China 3.Zhejiang Univ Technol, Hangzhou 310014, Zhejiang, Peoples R China;
推荐引用方式 GB/T 7714	Diao, Xingxing,Ma, Zhiyu,Wang, Haidong,et al. Simultaneous quantitation of 3-n-butylphthalide (NBP) and its four major metabolites in human plasma by LC-MS/MS using deuterated internal standards[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2013,78-79:19-26.
APA	Diao, Xingxing.,Ma, Zhiyu.,Wang, Haidong.,Zhong, Dafang.,Zhang, Yifan.,...&Chen, Xiaoyan.(2013).Simultaneous quantitation of 3-n-butylphthalide (NBP) and its four major metabolites in human plasma by LC-MS/MS using deuterated internal standards.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,78-79,19-26.
MLA	Diao, Xingxing,et al."Simultaneous quantitation of 3-n-butylphthalide (NBP) and its four major metabolites in human plasma by LC-MS/MS using deuterated internal standards".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 78-79(2013):19-26.