The sensitivity of the cis/trans-isomerization of enalapril and enalaprilat to solvent conditions

The cis‐ and trans‐isomers of enalapril and enalaprilat can be resolved by HPLC and by capillary electrophoresis. The isomeric content of enalapril is perturbed by the ionization of both its carboxyl and amine groups, while the isomeric content of enalaprilat is only perturbed by the ionization of i...

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Bibliographic Details
Published in:Journal of pharmacy and pharmacology 2005-07, Vol.57 (7), p.845-850
Main Authors: Ledger, Robin, Stellwagen, Earle
Format: Article
Language:English
Subjects:
Antihypertensive Agents - chemistry
Chromatography, High Pressure Liquid
Electrophoresis, Capillary
Enalapril - chemistry
Enalaprilat - chemistry
Isomerism
Solvents
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Summary:The cis‐ and trans‐isomers of enalapril and enalaprilat can be resolved by HPLC and by capillary electrophoresis. The isomeric content of enalapril is perturbed by the ionization of both its carboxyl and amine groups, while the isomeric content of enalaprilat is only perturbed by the ionization of its amine group. Increasing the hydrophobicity of the analyte solvent, as reflected in its molar polarization, increases the Z (cis) content of enalapril and markedly decreases the kinetics for isomerization. Far UV circular dichroic measurements suggest that the increase in Z (cis) content of enalapril is due to protonation of its carboxylate group. Taken together, the in‐vitro properties of enalapril and enalaprilat suggest that the in‐vivo transformation of the prodrug enalapril to the inhibitor enalaprilat and its delivery to angiotensin‐converting enzyme should not be significantly limited by cis/trans‐isomerization.
ISSN:0022-3573
2042-7158
DOI:10.1211/0022357056433