Evaluation of the immobilized artificial membrane phosphatidylcholine. Drug discovery column for high-performance liquid chromatographic screening of drug-membrane interactions.
Chromatographic retention factors (k') of a series of eight beta-adrenoceptor antagonist compounds (beta-adrenolytic drugs) were determined employing an immobilized artificial membrane column (IAM.PC.DD). The influence of mobile phase pH, ionic strength, and organic modifier composition was studied in order to examine column performance. After the IAM.PC.DD columns were exposed to approximately 7000 column volumes of a 0.01 M PBS mobile phase, five out of six columns tested showed significant peak broadening and decreased k' values indicative of premature column failure. The data suggested that the immobilized phospholipids stationary phase was removed by the 0.01 M PBS mobile phase. The beta-adrenolytic drug's log k'IAM values obtained with an IAM.PC.DD column were compared to an esterIAM.PC.MG column for predicting drug membrane interactions. For the linear regression analysis between log k'IAM and the logarithm of the n-octanol-water partition coefficients (rIAM.PC.DD = 0.8710 vs. rIAM.PC.MG = 0.9538), the C18 HPLC retention factors (rIAM.PC.DD = 0.8408 vs. rIAM.PC.MG = 0.9380), the liposome partition coefficients (rIAM.PC.DD = 0.8887 vs. rIAM.PC.MG = 0.9187), and various pharmacokinetic parameters, significantly better correlations were obtained with the esterIAM.PC.MG column than the IAM.PC.DD column.
Caldwell
G W
GW
R.W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477, USA.
Masucci
J A
JA
Evangelisto
M
M
White
R
R
D000070:Acebutolol / Q000032:analysis / Q000737:chemistry; D000097:Acetonitriles / Q000737:chemistry; D000319:Adrenergic beta-Antagonists / Q000032:analysis* / Q000737:chemistry; D000526:Alprenolol / Q000032:analysis / Q000737:chemistry; D000814:Aniline Compounds / Q000032:analysis / Q000737:chemistry; D001262:Atenolol / Q000032:analysis / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D008567:Membranes, Artificial; D008790:Metoprolol / Q000032:analysis / Q000737:chemistry; D008956:Models, Chemical; D009994:Osmolar Concentration; D010096:Oxprenolol / Q000032:analysis / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry*; D010869:Pindolol / Q000032:analysis / Q000737:chemistry; D011433:Propranolol / Q000032:analysis / Q000737:chemistry; D015203:Reproducibility of Results; D013999:Timolol / Q000032:analysis / Q000737:chemistry
D000097:Acetonitriles; D000319:Adrenergic beta-Antagonists; D000814:Aniline Compounds; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; C008625:nitroaniline; D001262:Atenolol; D010096:Oxprenolol; D000070:Acebutolol; D013999:Timolol; D000526:Alprenolol; D011433:Propranolol; D010869:Pindolol; D008790:Metoprolol; C032159:acetonitrile