Development of a method for determining related impurities in a new biologically active compound of cardioprotective action by capillary electrophoresis

Abstract

The original biologically active compound (BAS) N-[2-[4-oxo-3(4H)-quinazolinyl]propionyl]-guanidine (VMA-13-15), which has cardioprotective and neuroprotective activity, was synthesized on the basis of the FSUE at VolgSMU of the Ministry of Health of the Russian Federation. In accordance with the XIV State Pharmacopoeia of the Russian Federation, one of the criteria for quality control of pharmaceutical substances is the indicator "Related Impurities". Based on the synthesis scheme and the structure of the analyzed BAS as a technological impurity, we can assume the presence of the initial compound - - unsubstituted quinazoline-4(3H)-one, due to the possible incomplete flow of the reaction. Objective: the development and validation evaluation of the methodology for determining the technological impurity (quinazoline-4(3H)-one) to include it in the draft regulatory document for the proposed BAS VMA-13-15 as a pharmaceutical substance. Materials and methods. The capillary electrophoretic conditions proposed earlier by us for the determination of the BAS under study were chosen for the analysis, under which the compounds in question are well separated as clear peaks with a migration time of 6.59 min for N-[2-[4-oxo-3(4H)-quinazolinyl]propionyl]-guanidine and 4.37 min for quinazoline-4(3H)-one. Results. As a result of this research, the methodology for determining the indicator "Related Impurities" in BAS VMA-13-15 using capillary electrophoresis system was developed. The developed technique was validated in accordance with the requirements of SF RF of the XIV edition and proved to be acceptable for determination of the identified technological impurity quinazoline-4(3H)-one. Conclusion. The developed technique makes it possible to detect an impurity in the content of 0.1% or more.