Determination of perindopril and indapamide impurities in pharmaceuticals HPLC

Abstract

The objects of the study were antihypertensive drugs (AHD) - angiotensin-converting enzyme
inhibitor perindopril ((2S,3aS,7aS)-1-[(S)-N-[(S)-1-carboxybutyl]alanyl]hexahydro-2-indolinecarboxylic
acid, 1-ethyl ester) and the diuretic indapamide (4-сhloro-N-(2-methyl-1-indolinyl)-3-sulfamoylbenzamide),
as well as antihypertensive drug-based individual and combined preparations which contain impurities. The
chromatographic behavior of the investigated AHD was studied by reversed-phase HPLC with recourse to
eluent "phosphate buffer (pH 2.0) - acetonitrile". It was found that within the concentration range of 30-60%
of acetonitrile, the retention of perindopril and indopamide is described by displacement models of SnyderSochevinskiy
and Scott-Kuchera. The effect of the temperature on the retention factor, blurring zones and
separation of tested AHD was also studied. It was found that the most appropriate mode for the separation
and determination of perindopril, indapamide and their impurities is a gradient at 70°C. Selective and
sensitive methods were developed and validated for the quantitative determination of perindopril and
indapamide impurities in tablets of individual and combined preparations by reverse-phase HPLC with
spectrophotometric detection.