Chromatographic estimation of drug disposition properties by means of immobilized artificial membranes (IAM) and C18 columns.
Chromatographic retention measurement in immobilized artificial membranes (IAMs) is considered a fast and reliable method to predict biological properties (drug distribution) because of the IAM structure, which consists of phospholipid analogues bonded covalently to silica particles. A new parameter (d) is proposed to estimate the similarity between IAM columns, conventional HPLC columns, and drug distribution systems, and thus the performance of chromatographic systems to predict drug distribution. An IAM.PC.DD2 column has been used for this study, together with two XTerra columns (MSC18 and RP18), at several acetonitrile-water mobile phases. According to the d parameter, good correlations should be obtained between chromatographic systems (both IAM and C18) and octanol-water partition coefficient (log P), and thus both types of columns could be used to obtain log P values. The IAM.PC.DD2 system shows a close similarity to human skin partition, tadpole narcosis, and blood-brain permeability processes, showing that it can be useful as a model for these biological processes. Controversially, it is shown that human skin permeation is more similar to C18 partition than to IAM partition. Other biological processes such as blood-brain distribution and tissue-blood partition show a poor similarity to IAM and C18 systems, demonstrating that estimation of these drug distribution processes by chromatographic measurements may not be adequate.
Lázaro
Elisabet
E
Departament de Química Analítica, Universitat de Barcelona, Martí i Franquès 1, E-08028 Barcelona, Spain.
Ràfols
Clara
C
Abraham
Michael H
MH
Rosés
Martí
M
D000097:Acetonitriles; D000818:Animals; D001812:Blood-Brain Barrier; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation; D006801:Humans; D007408:Intestinal Absorption; D008567:Membranes, Artificial; D008954:Models, Biological; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry; D010599:Pharmacokinetics; D012822:Silicon Dioxide / Q000737:chemistry; D012869:Skin Absorption; D012997:Solvents; D014018:Tissue Distribution; D014867:Water
D000097:Acetonitriles; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D012997:Solvents; D014867:Water; D012822:Silicon Dioxide; C032159:acetonitrile