Current and future trends in the application of HPLC-MS to metabolite-identification studies

被引:78
作者
Castro-Perez, Jose M. [1 ]
机构
[1] Waters Corp, Milford, MA 01757 USA
关键词
D O I
10.1016/j.drudis.2007.01.007
中图分类号
R9 [药学];
学科分类号
1007 [药学];
摘要
Metabolic determinations are an integral part of every drug-discovery and drug-development program. Recent emphasis has been to increase sample throughput while, at the same time, increase information content within assays. To this end, screening for potential drug-drug interactions, overall metabolic stability and metabolite profiles are used early in discovery to select compounds for development. The throttle on the metabolism discovery engine is limited by the time required for data processing and reporting of the information-rich assays used in discovery-stage metabolism studies. In this article I examine how to increase throughput screening in drug discovery using novel liquid chromatography and mass spectrometry as the preferred analytical tool, and potential solutions to maximize Output.
引用
收藏
页码:249 / 256
页数:8
相关论文
共 41 条
[1]
Integration of knowledge-based metabolic predictions with liquid chromatography data-dependent tandem mass spectrometry for drug metabolism studies: Application to studies on the biotransformation of Indinavir [J].
Anari, MR ;
Sanchez, RI ;
Bakhtiar, R ;
Franklin, RB ;
Baillie, TA .
ANALYTICAL CHEMISTRY, 2004, 76 (03) :823-832
[2]
Drug metabolites in safety testing [J].
Baillie, TA ;
Cayen, MN ;
Fouda, H ;
Gerson, RJ ;
Green, JD ;
Grossman, SJ ;
Klunk, LJ ;
LeBlanc, B ;
Perkins, DG ;
Shipley, LA .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2002, 182 (03) :188-196
[3]
MASS-SPECTROMETRY IN THE ANALYSIS OF GLUTATHIONE CONJUGATES [J].
BAILLIE, TA ;
DAVIS, MR .
BIOLOGICAL MASS SPECTROMETRY, 1993, 22 (06) :319-325
[4]
Balogh MP, 2006, LC GC N AM, V24, P762
[5]
Interspecies in vitro metabolism of the phosphodiesterase-4 (PDE4) inhibitor L-454,560 [J].
Bateman, Kevin P. ;
Trimble, Laird ;
Chauret, Nathalie ;
Silva, Jose ;
Day, Stephen ;
Macdonald, Dwight ;
Dube, Daniel ;
Gallant, Michel ;
Mastracchio, Anthony ;
Perrier, Helene ;
Girard, Yves ;
Nicoll-Griffith, Deborah .
JOURNAL OF MASS SPECTROMETRY, 2006, 41 (06) :771-780
[6]
Increasing throughput and information content for in vitro drug metabolism experiments using ultra-performance liquid chromatography coupled to a quadrupole time-of-flight mass spectrometer [J].
Castro-Perez, J ;
Plumb, R ;
Granger, JH ;
Beattie, L ;
Joncour, K ;
Wright, A .
RAPID COMMUNICATIONS IN MASS SPECTROMETRY, 2005, 19 (06) :843-848
[7]
A high-throughput liquid chromatography/tandem mass spectrometry method for screening glutathione conjugates using exact mass neutral loss acquisition [J].
Castro-Perez, J ;
Plumb, R ;
Liang, L ;
Yang, E .
RAPID COMMUNICATIONS IN MASS SPECTROMETRY, 2005, 19 (06) :798-804
[8]
Advances in MS-based approaches for drug and metabolism studies [J].
Castro-Perez, J ;
Hoyes, J ;
Major, H ;
Preece, S .
CHROMATOGRAPHIA, 2002, 55 (Suppl 1) :S59-S63
[9]
Molecular imaging of thin mammalian tissue sections by mass spectrometry [J].
Chaurand, Pierre ;
Cornett, D. Shannon ;
Caprioli, Richard M. .
CURRENT OPINION IN BIOTECHNOLOGY, 2006, 17 (04) :431-436
[10]
Improving LC-MS sensitivity through increases in chromatographic performance: Comparisons of UPLC-ES/MS/MS to HPLC-ES/MS/MS [J].
Churchwell, MI ;
Twaddle, NC ;
Meeker, LR ;
Doerge, DR .
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2005, 825 (02) :134-143