Validação do método analítico de epicloridrina na matéria-prima de carvedilol

Abstract

is one of the drugs most used in the treatment of systemic arterial hypertension and control of associated cardiovascular diseases. The use of this drug is intended to reduce cardiovascular mortality in patients suffering from myocardial infarction, heart failure and left ventricular dysfunction. In the documentation evaluation of this active synthesis process, it is verified the presence of epichlorohydrin, which is an impurity and presents genotoxic alert. According with Guideline in the Limits of Genotoxic Impurities, the limit of epichlorohydrin presence is 15 ppm. In the present work, a method of quantification of epichlorohydrin was validated by gas chromatography (GC), using the flame ionized detector (FID) coupled to the headspace sampler. A G16 column with 30 m x 0.53 mm x 2.0 μm, 4.0 mL min-1 drag gas flow and 1: 2 ratio split injection was used. The performed validation complied with the parameters described in current Brazilian legislation RDC166 / 2017. The method used has been shown to be specific, linear, precise, accurate and robust and therefore suitable for the quantification of the epichlorohydrin impurity in the raw material of carvedilol.