Evaluation of the retention of antihypertensive drugs in ultra high performance Supercritical Fluid Chromatography and methods development using chemometric tools

Abstract

Ultra High Performance Supercritical Fluid Chromatography (UHPSFC) is a novel analytical technique that emerged worldwide since the release of the first commercial instruments, in 2012. This technique employs a gas in the supercritical state as the mobile phase (usually carbon dioxide, CO2) associated with small amounts of organic solvents (1-30%), added to modify its selectivity. Due to the low viscosity of the mobile phase, it is possible to use higher flow rates, enabling faster analysis with high chromatographic efficiency. All these features lead to significant reduction in the consumption of solvents, which is consistent with the principles of "Green Chemistry". The composition of the stationary and mobile phases associated with the conditions of temperature and pressure control retention in this technique in a complex and yet poorly understood way, being the key points to its future development. This project aims to better understand the retention of analytes with different physicochemical properties according to the mentioned experimental variables. The selected analytes are the anti-hypertensive drugs atenolol, propranolol, losartan, chlorthalidone and hydrochlorothiazide, due to their great economic importance nationally and internationally and their broad polarity range. These drugs can be used separately or in association, in the so-called combined therapy, widely used in cases of hypertension. Owing to interactions between the experimental variables, multivariate methods of Design of Experiments (DOE) will be associated with the analytical development to obtain mathematical models that describe the retention of the analytes according to the experimental conditions. This approach has been highly encouraged at the international level, as shown by the introduction of the initiative called Analytical Quality by Design (A-QbD) by regulatory agencies in the pharmaceutical area.