Quantitative relationships between the structure of beta-adrenolytic and antihistamine drugs and their retention on an alpha 1-acid glycoprotein HPLC column.
Chromatographic retention parameters of a series of 7 beta-adrenolytics and of 12 antihistamine drugs were determined employing an alpha 1-acid glycoprotein (AGP) high-performance liquid chromatographic (HPLC) column. For the group of antihistamines capillary electrophoretic (CE) retention was additionally measured in the presence of either AGP or human serum albumin (HSA). Two series of solutes hydrophobicity parameters were obtained by reversed-phase HPLC on an immobilized artificial membrane (IAM) column. The solutes studied were subjected to molecular modelling and the structural descriptors obtained were applied in studies of quantitative structure-retention (protein binding) relationships (QSRR). It was found that retention on AGP correlates well with the literature on physiological protein binding data. This retention was demonstrated to depend on hydrophobicity: to a lesser extent in the case of beta-adrenolytics and strongly in the case of antihistamines. Hydrophobicity, along with molecular width and electron excess charge on aliphatic nitrogen was demonstrated to describe retention of antihistamines on AGP. The AGP column is recommended as a convenient reactor for studies of drug-protein interactions. Preliminary CE data do not correlate with the HPLC data.
Nasal
A
A
Department of Biopharmaceutics and Pharmacodynamics, Medical Academy of Gdańsk, Poland.
Radwańska
A
A
Ośmiałowski
K
K
Buciński
A
A
Kaliszan
R
R
Barker
G E
GE
Sun
P
P
Hartwick
R A
RA
D000319:Adrenergic beta-Antagonists / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D004586:Electrophoresis; D006634:Histamine H1 Antagonists / Q000737:chemistry* / Q000378:metabolism; D008790:Metoprolol; D009961:Orosomucoid / Q000378:metabolism*; D010869:Pindolol; D012044:Regression Analysis; D013329:Structure-Activity Relationship
D000319:Adrenergic beta-Antagonists; D006634:Histamine H1 Antagonists; D009961:Orosomucoid; D010869:Pindolol; D008790:Metoprolol