A very important class of antihypertensive drugs are angiotensin converting enzyme (ACE) inhibitors. They are generally known as the prils. Most of ACE inhibitors are administrated into the body as prodrugs; chemically they are monoesters of diacids which metabolize to real enzyme inhibitors - diacids, which are called prilates.

It is well known from NMR studies that both, priles and prilates, as a substituted ami­des, can exist in solution as cis and trans rotamers and may interconvert around the amide bond (see for example, rotamers of ramipril and ramiprilat).

Recently, it has been surprisingly found that during HPLC analysis the cis-trans interconversion can also proceed, which influences the peak shape or even causes peak splitting.

In our laboratory the chromatographic behaviour of some ACE inhibitors (prils and prilates) was studied. We worked out mobile phases in which cis-trans rotamers may be observable. We also studied how column temperature influences rotamers separation and the rate of isomerization. Simultaneously, preliminary NMR studies were carried out for solving the structure of rotamers and establishing which rotational isomer dominates in solution.

These investigations are crucial for proper determination of studied ACE inhibitors in mixture. The cis-trans isomerization process observed under HPLC condition can lead to misinterpretation of the identity of a peak, because peak broadening or even splitting can be easily attributed to an impurity. This should be taken into account when describing ACE inhibitors and their metabolism products in Pharmacopoeia.

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