Chemical compounds containing chiral centers in their molecules show optical isomerism.  Angiotensin converting enzyme inhibitors (ACE inhibitors) used in arterial hypertension treatment is a large group of medical substances containing chiral centers.

     One of them - benazepril hydrochloride contains two stereogenic centers, but is currently available as single enantiomer (S,S configuration) for the treatment of hypertension. Its enantiomer (R,R configuration) and the diastereoisomeric pair ( R,S and S,R) can be regarded as impurities.     

      The aim of this study was to estimate stereochemical stability of S,S isomer of benazepril hydrochloride as well as examining their potential susceptibility to conversion in the active substance and in Lisonid tablets.

       At the first stage of the study the chromatographic methods of separation of examined enantiomers were explored applying TLC and HPLC methods.

The best separation with the use of the TLC method was obtained the following system: chromatographic plates Chiralplate and a mobile phase methanol – acetonitrile - 1mM copper (II) acetate (4:2:4) with saturation of glacial acetic acid for 1 hour.

For the separation with the HPLC method numerous chiral columns as well as mobile phases were tested. The system, described in Ph.Eur., proved to be the best one: Chiral AGP column (150mm x 4,0mm x 5μm) and a mobile phase: phosphate buffer pH=6,0 – methanol (80:20), column temperature: 30°C, flow rate: 0,9 ml/min, wavelength λ=240 nm.

The system was subsequently used for examination of stereochemical stability of benazepril hydrochloride in the substance and Lisonid – coated tablets 20 mg.

The active substance - benazepril hydrochloride and coated tablets Lisonid 20 mg were  subjected to the impact of different stress factors: temperature of 40°C, 1 N sodium hydroxide solution and temperature of 40°C, 0,05 N sodium hydroxide solution and temperature of 40 °C, 1 N hydrochloric acid solution and temperature of 40°C, 6% hydrogen peroxide solution and temperature of 40°C and 1000 watt UV light, 3 times each 10 minutes.

Tests were carried out after 1 and 6 weeks.

  It was found that none of the applied stress factors caused the transformation of SS enantiomer of benazepril hydrochloride in the substance and tablets to other identified stereoisomers - only the compound decomposition has occurred.

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