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In vitro permeability of eight β‐blockers through Caco‐2 monolayers utilizing liquid chromatography/electrospray ionization mass spectrometry
Author(s) -
Caldwell Gary W.,
Easlick Scott M.,
Gunnet Joseph,
Masucci John A.,
Demarest Keith
Publication year - 1998
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/(sici)1096-9888(199807)33:7<607::aid-jms672>3.0.co;2-o
Subject(s) - chemistry , chromatography , electrospray ionization , mass spectrometry , caco 2 , liquid chromatography–mass spectrometry , analyte , electrospray , analytical chemistry (journal) , in vitro , biochemistry
It is demonstrated that the apparent permeability ( P app ) coefficients of β‐adrenoceptor antagonist drugs can easily 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 P app coefficients of β‐adrenoceptor antagonists determined by LC/MS have the same ranking order as those determined by LC/UV and radioactivity assays. However, the P app coefficients determined in this study showed significant discrepancies from those determined in other laboratories. There are several experimental factors that directly affect the absolute value of the P app coefficients, including pH gradients, additional diffusion barriers (i.e. unstirred water layer and type of filter support), analyte concentration, detection method and possibly cell culture variations. These parameters should be controlled when generating Caco‐2 P app coefficients for different compounds. © 1998 John Wiley & Sons, Ltd.