'LC-electrolyte effects' improve the bioanalytical performance of liquid chromatography/tandem mass spectrometric assays in supporting pharmacokinetic study for drug discovery
文献类型：期刊论文
| 作者 | 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
 |
| 出版日期 | 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 |
| WOS记录号 | WOS:000248769800005 |
| 出版者 | WILEY-BLACKWELL |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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