title: 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, logk(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 logD value at the isoelectric point. However, logk(w) could be successfully converted to logD by means of a calibration equation established for ionized acidic compounds.
authors.affiliation: School of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimiopolis, Zografou, Athens 157 71, Greece.
authors.forename: Spyros
authors.initials: S
authors.lastname: Gikas
authors.forename: Fotios
authors.initials: F
authors.lastname: Tsopelas
authors.forename: Costas
authors.initials: C
authors.lastname: Giaginis
authors.forename: John
authors.initials: J
authors.lastname: Dimitrakopoulos
authors.forename: Theodora
authors.initials: T
authors.lastname: Livadara
authors.forename: Helen
authors.initials: H
authors.lastname: Archontaki
authors.forename: Anna
authors.initials: A
authors.lastname: Tsantili-Kakoulidou
mesh_terms: D017738:Alkanesulfonic Acids / Q000737:chemistry; D000959:Antihypertensive Agents / Q000032:analysis*; D002021:Buffers; D002138:Calibration; D055598:Chemical Phenomena; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004656:Enalapril / Q000032:analysis* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007526:Isoelectric Point; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry; D000442:Octanols / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D017738:Alkanesulfonic Acids; D000959:Antihypertensive Agents; D002021:Buffers; D009025:Morpholines; D000442:Octanols; D014867:Water; C068559:propylsulfonic acid; D004656:Enalapril; C037574:morpholine