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

✍ Scribed by Hai-Zhi Bu; Marzena Poglod; Ronald G. Micetich; Jehangir K. Khan

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 66 KB
• Volume: 14
• Category: Article
• ISSN: 0951-4198
• DOI: 10.1002/(sici)1097-0231(20000331)14:6<523::aid-rcm906>3.0.co;2-t

✦ Synopsis

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.