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

• Published in: Rapid communications in mass spectrometry Vol. 14; no. 6; pp. 523 - 528
• Main Authors: Bu, Hai-Zhi, Poglod, Marzena, Micetich, Ronald G., Khan, Jehangir K.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 31-03-2000
• Subjects: Caco-2 Cells; Cell Membrane Permeability; Chemical Phenomena; Chemistry, Physical; Humans; Mass Spectrometry; Reference Standards
• ISSN: 0951-4198; 1097-0231
• DOI: 10.1002/(SICI)1097-0231(20000331)14:6<523::AID-RCM906>3.0.CO;2-T

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. Copyright © 2000 John Wiley & Sons, Ltd.