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

Rapid Commun Mass Spectrom. 2000;14(6):523-8. 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.

MeSH terms

  • Caco-2 Cells
  • Cell Membrane Permeability*
  • Chemical Phenomena
  • Chemistry, Physical
  • Humans
  • Mass Spectrometry
  • Reference Standards