Chromatographic behavior of zwitterionic enalapril—Exploring the conditions for lipophilicity assessment

Abstract

The chromatographic behavior of enalapril was investigated under different stationary and mobile phase conditions in an effort to unravel interferences in the underlying retention mechanism, which would affect its relation to octanol–water partitioning. Extrapolated retention factors, log k w, were used as relevant chromatographic indices. The retention/pH profile was established and the peak split phenomenon, associated with cis/ trans interconversion, was also monitored as a function of pH. The pH at maximum retention and minimum peak split occurrence was chosen for further investigation, so that the presence of zwitterionic structure was guaranteed and any effect of cis/ trans interconversion could be ignored. Retention of zwitterionic enalapril was found to be very sensitive to mobile phase conditions in regard to organic modifier as well to the aqueous component. The use of morpholine-propanesulfonic acid (MOPS) as buffer and the presence of n-octanol as mobile phase additive proved critical factors for maximum suppression of secondary interactions. Nevertheless, the corresponding extrapolated retention factor was considerably larger than octanol–water log D value at the isoelectric point. However, log k w could be successfully converted to log D by means of a calibration equation established for ionized acidic compounds.