Study of the cis-trans isomerization of enalapril by reversed-phase liquidchromatography

Enalapril is a dipeptidic angiotensin converting enzyme inhibitor. It exist s as a mixture of two conformers in solution with respect to the peptide bo nd involving the proline amino group. The RPLC of such products may yield p eak splitting or multiple peaks as a result of the slow kinetics of the con formation change. In this study, the influence of the flow-rate, pH, temper ature, organic modifier and counter ion on the peak shape and the separatio n of the cis and trans conformers are examined qualitatively by HPLC. It ap pears that decrease of relaxation time for isomerization with concomitant i mprovement in peak shape is favoured by a decrease in pH and flow-rate, inc rease of temperature, choice of organic solvent (nature, amount) and cation ic counter ion concentration in the mobile phase. The elution order of the isomers was dependent on the nature of the organic modifier whereas the sep aration selectivity was improved by an increase of pH or the addition of a negatively charged counter ion. In addition, an NMR investigation on enalap ril is described. (C) 2000 Elsevier Science B.V. All rights reserved.