Investigation of the Rotational Isomerism of Quinapril and Quinaprilat by UPLC-DAD and Elucidation of the Conformational Equilibrium by NMR.

Abstract : Quinapril and quinaprilat are two angiotensin-converting enzyme inhibitors (ACEIs) characterized by a peak broadening and splitting when they were analyzed by ultra-performance liq. chromatog. (UPLC). This phenomenon is due to the existence of the two isomers cis and trans around the amide band. In order to confirm the existence of the two conformers and allow identification of the predominant form, NMR studies of quinapril, involving 1H, 13C, 1H-1HCOSY, Impact-HMBC, JMOD, HSQC, and ROESY have been conducted in this work. The analyses allowed us to identify the predominant form of quinapril; the conformer trans is the predominant form (75%). In addn., this study highlights the important benefits of UPLC to sep. quinapril and quinaprilat isomers due to its high resolving power. The effect of various operating conditions on the retention peak, namely, splitting and band broadening of quinaprilat and quinapril, has been qual. examd. in this study. Several practical exptl. conditions have been tested, allowing both the elution of the two ACEIs as single peaks, while keeping at the same time an acceptable sepn. The effect of various factors on the conformational s-cis-s-trans equil. of quinapril and quinaprilat, namely, the compn. of the mobile phase, column temp., flow rate, pH, and type and amt. of org. modifier was investigated by UPLC-DAD (diode array detector) with a BEH C18 column (100mm, 2.1mm internal diam.×1.7μm particle diam.). Several deconvolution models were used to model overlapped peaks and to det. resoln. Results obtained showed that a mobile phase consisting of ammonium buffer (10mM; pH 8) and acetonitrile allows the sepn. of the quinapril and quinaprilat conformers. Maximum resoln. was obtained for a compn. of mobile phase (55/45) and (65/35) (ammonium buffer/acetonitrile, vol./vol.) for quinapril and quinaprilat, resp. at 45°C and flow rates of 0.4 and 0.5mLmin-1.
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Submitted on : Thursday, May 21, 2015 - 1:14:55 PM
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Maha Dendeni, Nicolas Cimetiere, Isabelle Soutrel, Jean Paul Guegan, Najib Ben Hamida, et al.. Investigation of the Rotational Isomerism of Quinapril and Quinaprilat by UPLC-DAD and Elucidation of the Conformational Equilibrium by NMR.. Australian Journal of Chemistry, CSIRO Publishing, 2015, 68, pp.783--792. ⟨10.1071/CH14312⟩. ⟨hal-01154215⟩

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