Counter-current chromatographic estimation of hydrophobicity of Z-(cis) and E-(trans) enalapril and kinetics of cis/trans isomerization.
The kinetics of Z-(cis)/E-(trans) isomerization of enalapril was investigated by reversed phase high-performance liquid chromatography (RP-HPLC) using a monolith ODS column under a series of different temperature and pH conditions. At a neutral pH 7, the rate (k(obs)) of Z-(cis)/E-(trans) isomerization of enalapril at 4 degrees C (9.4 x 10(-3)min(-1)) is much lower than at 23 degrees C (1.8 x 10(-1)min(-1)), while the fractional concentration of Z-(cis) isomer is always higher than that of E-(trans) isomer in the pH range 2-7. The fractional concentration of the E-(trans) isomer becomes a maximum (about 40%) in the pH range 3-6, where enalapril exists as a zwitterion. The hydrophobicity (logP(O/W)) of both isomers was estimated by high-speed counter-current chromatography (HSCCC). Normal phase HSCCC separation using a tert-butyl methyl ether-acetonitrile-20mM potassium phosphate buffer (pH 5) two-phase solvent system (2:2:3, v/v/v) at 4 degrees C was effective in partially separating the isomers, and the partition coefficient (K) of each isomer was directly calculated from the retention volume (V(R)). The logP(O/W) values of Z-(cis) and E-(trans) isomers were -0.46 and -0.65, respectively.
Shoji
Atsushi
A
Division of Structural Biology and Analytical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Yanagida
Akio
A
Shindo
Heisaburo
H
Ito
Yoichiro
Y
Shibusawa
Yoichi
Y
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003377:Countercurrent Distribution / Q000379:methods*; D004656:Enalapril / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007536:Isomerism; D007700:Kinetics
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril