Integrated high capacity solid phase extraction-MS/MS system for pharmaceutical profiling in drug discovery

被引:21
作者
Kerns, EH
Kleintop, T
Little, D
Tobien, T
Mallis, L
Di, L
Hu, M
Hong, Y
McConnell, OJ
机构
[1] Wyeth Ayerst Res, Princeton, NJ 08543 USA
[2] Micromass, Manchester, Lancs, England
[3] LEAO Technol, Carrboro, NC USA
[4] Wyeth Ayerst Res, Collegeville, PA USA
关键词
drug discovery; stability; high throughput; MS/MS; on-line solid phase extraction; screening; pharmaceutical profiling;
D O I
10.1016/j.japna.2003.03.001
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
A method is described for use in analysis of samples from pharmaceutical profiling of early drug discovery compounds. The method consists of a high capacity autosampler which injects samples into one of two solid phase extraction columns operated in parallel for alternating trapping, washing and elution into a tandem quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) MS/MS mode. A primary method, which is useful for 80-90% of compounds, and a secondary method, which is useful for a majority of the remaining compounds, are described. No analytical HPLC column is used and the analysis rate is approximately 50 samples/h. Specificity is obtained using MRM analysis. Application of the method for high capacity analysis of metabolic stability samples is described. (C) 2003 Elsevier B.V. All rights reserved.
引用
收藏
页码:1 / 9
页数:9
相关论文
共 15 条
[1]  
ACKERMANN BL, 2002, AM PHARM REV, V5, P54
[2]   High-throughput cytochrome P450 (CYP) inhibition screening via a cassette probe-dosing strategy - V. Validation of a direct injection/on-line guard cartridge extraction-tandem mass spectrometry method for CYP1A2 inhibition assessment [J].
Bu, HZ ;
Knuth, K ;
Magis, L ;
Teitelbaum, P .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2001, 12 (04) :447-452
[3]   MASS-SPECTROMETRY MASS-SPECTROMETRY [J].
COOKS, RG ;
GLISH, GL .
CHEMICAL & ENGINEERING NEWS, 1981, 59 (48) :40-52
[4]   High-speed gradient parallel liquid chromatography/tandem mass spectrometry with fully automated sample preparation for bioanalysis: 30 seconds per sample from plasma [J].
Deng, Y ;
Wu, JT ;
Lloyd, TL ;
Chi, CL ;
Olah, TV ;
Unger, SE .
RAPID COMMUNICATIONS IN MASS SPECTROMETRY, 2002, 16 (11) :1116-1123
[5]   High-throughput liquid chromatography ultraviolet/mass spectrometric analysis of combinatorial libraries using an eight-channel multiplexed electrospray time-of-flight mass spectrometer [J].
Fang, L ;
Cournoyer, J ;
Demee, M ;
Zhao, J ;
Tokushige, D ;
Yan, B .
RAPID COMMUNICATIONS IN MASS SPECTROMETRY, 2002, 16 (15) :1440-1447
[6]   A high capacity LC/MS system for the bioanalysis of samples generated from plate-based metabolic screening [J].
Janiszewski, JS ;
Rogers, KJ ;
Whalen, KM ;
Cole, MJ ;
Liston, TE ;
Duchoslav, E ;
Fouda, HG .
ANALYTICAL CHEMISTRY, 2001, 73 (07) :1495-1501
[7]  
Johnson J. V., 1985, ANAL CHEM, V57, P758
[8]   Pharmaceutical profiling in drug discovery [J].
Kerns, EH ;
Di, L .
DRUG DISCOVERY TODAY, 2003, 8 (07) :316-323
[9]  
KERNS EH, 2001, J PHARM SCI, V2, P87
[10]  
Korfmacher WA, 1999, RAPID COMMUN MASS SP, V13, P1991, DOI 10.1002/(SICI)1097-0231(19991030)13:20<1991::AID-RCM743>3.3.CO