Determination of distribution coefficients for some 5-HT3 receptor antagonists by reversed-phase high-performance liquid chromatography.
It is of major interest to determine the physico-chemical properties, dissociation constants and lipophilicity of potential drugs owing to their implication in absorption mechanisms. The HPLC capacity factors appear to be attractive and readily accessible lipophilic parameters. An isocratic HPLC method was designed using a C8 column to determine the relative lipophilicity for two sets of 5-HT3 receptor antagonists, including tropine and quinolizine analogues. Dimethyloctylamine was added to the eluent to mask silanophilic interactions and lead to a predominant partitioning mechanism. The capacity factors determined by a monocratic procedure showed good correlations with the distribution coefficients obtained by the shake-flask method, showing the validity of capacity factors as lipophilicity descriptors for close analogues.
Marion Merrell Dow Research Institute, Strasbourg, France.
C
C
Kugel
B
B
Heintzelmann
J
J
Wagner
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D011807:Quinolizines / Q000737:chemistry; D012702:Serotonin Antagonists; D012995:Solubility; D014326:Tropanes / Q000737:chemistry
D007202:Indicators and Reagents; D011807:Quinolizines; D012702:Serotonin Antagonists; D014326:Tropanes