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Chromatographic modelling of interactions between melanin and phenothiazine and dibenzazepine drugs
Author(s) -
Radwa Aleksandra,
Fra̧ckowiak Teresa,
Ibrahim Houda,
Aubry AnneFrançoise,
Kaliszan Roman
Publication year - 1995
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.1130090509
Subject(s) - chemistry , phenothiazine , chromatography , melanin , ultrafiltration (renal) , molecular descriptor , column chromatography , quantitative structure–activity relationship , stereochemistry , medicine , biochemistry , pharmacology
Differences in drug‐melanin interactions were determined for 13 phenothiazine neuroleptics and 2 dibenzazepine thymoleptics by means of high‐performace liquid chromatography. The chromatographic column was packed with a stationary phase obtained by chemical immobilization of synthetic L ‐dopa melanin on silica particles. For six phenothiazines the melanin‐binding parameters were also determined by an ultrafiltration method. Correlation between measures of drug‐melanin interaction determined chromatographically and by the standard slow‐equilibrium method was significant, however moderate. The chromatographic method of assessing interactions between drugs‐melanin interaction determined chromatographically and by the standard slow‐equilibrium method was significant, however moderate. The chromatographic method of assessing interactions between drugs and melanin permitted reliable and quantitatively comparable data for representative series of solutes to be readily obtained. Such data were subjected to the analysis of quantitative structure‐retention relationships (QSRR). It was found that retention of the agents on the immobilized melanin column could be described by two‐parameter regression equations comprising the energy of the lowest unoccupied molecular orbital and either the water‐accessible surface area of a drug molecule or its hydrophobicity parameter, determined chromatographically on an immobilized artificial membrane column. The QSRR equation derived allows for the estimation of melanin binding based on the structure of a compound candidate, and thus rationalizes predictions of potential toxicity of drugs or drug candidates.