In vitro permeability of eight β-blockers through Caco-2 monolayers utilizing liquid chromatography/electrospray ionization mass spectrometry

✍ Scribed by Caldwell, Gary W.; Easlick, Scott M.; Gunnet, Joseph; Masucci, John A.; Demarest, Keith

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 288 KB
• Volume: 33
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/(sici)1096-9888(199807)33:7<607::aid-jms672>3.0.co;2-o

✦ Synopsis

It is demonstrated that the apparent permeability coefficients of b-adrenoceptor antagonist drugs can easily (P app ) be determined for Caco-2 cell culture intestinal models utilizing liquid chromatography/mass spectrometry (LC/MS). The LC/MS method with electrospray ionization in the single ion monitoring mode showed an increased sensitivity of 1000-fold compared with LC/UV detection and enhanced selectivity with respect to both LC/UV and radioactivity assays. The coefficients of b-adrenoceptor antagonists determined by LC/MS have the same P app ranking order as those determined by LC/UV and radioactivity assays. However, the coefficients determined P app in this study showed signiÐcant discrepancies from those determined in other laboratories. There are several experimental factors that directly a †ect the absolute value of the coefficients, including pH gradients, additional P app di †usion barriers (i.e. unstirred water layer and type of Ðlter support), analyte concentration, detection method and possibly cell culture variations. These parameters should be controlled when generating Caco-2 coefficients for P app di †erent compounds.