In vivo drug screening

Olah, T. V., McLoughlin, D. A., Gilbert, J. D., The simultaneous determination of mixtures of drug candidates by liquid chromatography/ atmospheric pressure chemical ionisation mass spectrometry as an in-vivo drug screening procedure, Rapid Commun. Mass Spec. 1997, 11, 17—23. 

Qlah, T.V. McLoughlin, D.A. Gilbert, J.D. The Simultaneous Determination of Mixtures of Drug Candidates by Liquid Chromatography/Atmospheric Pressure Chemical Ionization Mass Spectrometry as an In Vivo Drug Screening Procedure, Rapid Commun. Mass Spectrom. 11,17-23 (1997). 

Beaudry F. et al., 1998. In vivo pharmacokinetic screening in cassette dosing experiments Use of online Pros-pekt liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry technology in drug discovery. Rapid Commun Mass Spectrom 12 1216. 

Meador V, Jordan W, Zimmermann J. Increasing throughput in lead optimization in vivo toxicity screens. Curr. Opin. Drug Discov. Devel. 2002 5 72-78. 

Because of these limitations, the NCI in 1989 changed to a rationally designed "disease-oriented" screening panel incorporating 60 cell lines derived from a variety of different human solid tumors (69). Currently, this cell line screen is a key component of the NCTs comprehensive in vitro and in vivo preclinical screening and drug development program. 

Beaudry, E LeBlanc, J.Y.C. Coutu, M. Brown, N. In Vivo Pharmcokinetic Screening in Cassette Dosing Experiments The Use of On-Line Prospekt Liquid Chromatography/Atmospheric Pressure Chemical Ionization Tandem Mass Spectrometry Technology in Drug Discovery, Rapid Commun. Mass Spectrom. 12, 1216-1222 (1998). 

To answer these needs, a series of in vitro and in vivo assays have been developed with the goal of providing these data in a time frame that is compatible with the requirements of medicinal chemists who are making the new chemical entities (NCEs). Most of the in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) screens use LC-MS or LC-MS/MS for the analytical step. As shown in Figure 12.1, one approach for using these assays is to view the process of lead optimization as passing the lead... 

Liu, B. et al., Snapshot PK A rapid rodent in vivo preclinical screening approach, Drug Discov. Today, 13(7-8), 360, 2008. 

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