title: High-throughput caco-2 cell permeability screening by cassette dosing and sample pooling approaches using direct injection/on-line guard cartridge extraction/tandem mass spectrometry.
abstract: A method for high-throughput Caco-2 permeability screening of drug candidates has been developed using thirteen generic drugs as test compounds. The high throughput was achieved by either a sample pooling or a cassette dosing approach, along with the use of a rapid, simple and sensitive direct injection/on-line guard cartridge extraction/tandem mass spectrometric assay that was also developed in this study. It was of concern that possible drug-drug interactions (e.g., inhibition of P-glycoprotein-mediated transport of a drug by another, and/or competition of the drugs for transport pathways), when the cassette dosing regimen was implemented, may give rise to inconsistent results compared with those attained by a traditional single-drug dosing approach. However, the apparent permeability coefficients of the test drugs across Caco-2 monolayers measured by the sample pooling or cassette dosing (up to five drugs co-administered in this study) strategy were in good conformity with the data obtained by single-drug dosing followed by discrete sample analysis.
authors.affiliation: Division of Biopharmaceutics and Pharmacokinetics, NAEJA Pharmaceutical, Inc., 4290-91A Street, Edmonton, Alberta T6E 5V2, Canada.
authors.forename: H Z
authors.initials: HZ
authors.lastname: Bu
authors.forename: M
authors.initials: M
authors.lastname: Poglod
authors.forename: R G
authors.initials: RG
authors.lastname: Micetich
authors.forename: J K
authors.initials: JK
authors.lastname: Khan
mesh_terms: D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D013058:Mass Spectrometry; D012015:Reference Standards