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Title: Novel generic UPLC/MS/MS method for high throughput analysis applied to permeability assessment in early Drug Discovery
Authors: Mensch, Jurgen ×
Noppe, Mark
Adriaensen, Jef
Melis, Anouche
Mackie, Claire
Augustijns, Patrick
Brewster, Marcus E #
Issue Date: Mar-2007
Series Title: Journal of Chromatography B vol:847 issue:2 pages:182-187
Abstract: A novel generic ultra performance liquid chromatography-tandem mass spectrometric (UPLC/MS/MS) method for the high throughput quantification of samples generated during permeability assessment (PAMPA) has been developed and validated. The novel UPLC/MS/MS methodology consists of two stages. Firstly, running a 1.5min isocratic method, compound-specific multiple reaction monitoring (MRM) methods were automatically prepared. In a second stage, samples were analyzed by a 1.5min generic gradient UPLC method on a BEH C18 column (50mmx2.1mm). Compounds were detected with a Waters Micromass Quattro Premier mass spectrometer operating in positive electrospray ionization using the compound-specific MRM methods. The linearity for the validation compounds (caffeine, propranolol, ampicillin, atenolol, griseofulvin and carbamazepine) typically ranges from 3.05nM to 12,500nM and the limits of detection for all generically developed methods are in the range between 0.61nM and 12nM in an aqueous buffer. The novel generic methodology was successfully introduced within early Drug Discovery and resulted in a four-fold increase of throughput as well as a significant increase in sensitivity compared to other in-house generic LC/MS methods.
ISSN: 1570-0232
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Drug Delivery and Disposition
× corresponding author
# (joint) last author

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