'LC-electrolyte effects' improve the bioanalytical performance of liquid chromatography/tandem mass spectrometric assays in supporting pharmacokinetic study for drug discovery

doi:10.1002/rcm.3129

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	'LC-electrolyte effects' improve the bioanalytical performance of liquid chromatography/tandem mass spectrometric assays in supporting pharmacokinetic study for drug discovery
	Wang, Li ; Sun, Yan ; Dul, Feifei ; Niu, Wei ; Lu, Tong ; Kan, Jingmin ; Xu, Fang ; Yuan, Kaihong ; Qin, Tao ; Liu, Changxiao
刊名	RAPID COMMUNICATIONS IN MASS SPECTROMETRY
	2007
卷号	21 期号:16 页码:2573-2584
ISSN号	0951-4198
DOI	10.1002/rcm.3129
文献子类	Article
英文摘要	The development of rapid and sensitive bioanalytical methods in a short time frame with acceptable levels of precision and accuracy is imperative for successful drug discovery. We previously reported that the use of a mobile phase containing an extremely low concentration of ammonium formate or formic acid increased analyte electrospray ionization (ESI) response and controlled against matrix effects. We designated these favorable effects 'LC-electrolyte effects'. In order to support rapid pharmacokinetic (PK) studies for drug discovery, we applied LC-electrolyte effects to the development of generic procedures that can be used to quickly generate reliable PK data for compound candidates. We herein demonstrate our approach using four model tested compounds (Compd-A, -B, -C, and -D). The analytical methods involve generic protein precipitation for sample clean-up, followed by application of fast liquid chromatographic (LC) gradients and the subsequent use of electrospray ionization tandem mass spectrometry (ESI-MS/MS) for individual measurement of the tested compounds in 20-mu L plasma samples. Good linearity over the concentration range of 1.6 or 8-25000 ng/mL (r(2) > 0.99), precision (RSD, 0.45-13.1%), and accuracy (91-112%) were achieved through the use of a low dose of formic acid (0.4 mM or 0.015%.) in the methanol/water-based LC mobile phase. The analytical method was quite sensitive, providing a lower limit of quantification of 1.6 pg on-column except for Compd-C (8 pg), and showed negligible ion suppression caused by matrix components. Finally, the assay suitability was demonstrated in simulated discovery PK studies of the tested compounds with i.v./p.o. dosing of rats. This new assay approach has been adopted with good results in our laboratory for many recent discovery PK studies. Copyright (c) 2007 John Wiley & Sons, Ltd.
WOS关键词	ELECTROSPRAY ; THROUGHPUT ; METABOLISM ; PLASMA ; ABSORPTION ; OPTIMIZATION ; PARAMETERS ; SAMPLES ; MODEL
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry ; Spectroscopy
语种	英语
出版者	WILEY-BLACKWELL
WOS记录号	WOS:000248769800005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273417]
专题	上海药物代谢研究中心
通讯作者	Li, Chuan
作者单位	1.Jiangsu Hengrui Med Co Ltd, Jiansu 222002, Peoples R China 2.Tianjin Inst Pharmaceut Res, Tianjin State Key Lab Pharmacodynam & Pharmacokin, Tianjin 300193, Peoples R China 3.Chinese Acad Sci, SIBS, Shanghai Inst Mat Med, Shanghai Ctr DMPK Res,Grad Sch, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wang, Li,Sun, Yan,Dul, Feifei,et al. 'LC-electrolyte effects' improve the bioanalytical performance of liquid chromatography/tandem mass spectrometric assays in supporting pharmacokinetic study for drug discovery[J]. RAPID COMMUNICATIONS IN MASS SPECTROMETRY,2007,21(16):2573-2584.
APA	Wang, Li.,Sun, Yan.,Dul, Feifei.,Niu, Wei.,Lu, Tong.,...&Li, Chuan.(2007).'LC-electrolyte effects' improve the bioanalytical performance of liquid chromatography/tandem mass spectrometric assays in supporting pharmacokinetic study for drug discovery.RAPID COMMUNICATIONS IN MASS SPECTROMETRY,21(16),2573-2584.
MLA	Wang, Li,et al."'LC-electrolyte effects' improve the bioanalytical performance of liquid chromatography/tandem mass spectrometric assays in supporting pharmacokinetic study for drug discovery".RAPID COMMUNICATIONS IN MASS SPECTROMETRY 21.16(2007):2573-2584.