Determinação de fármacos antieméticos em amostras de sedimento usando microextração líquido-líquido assistida pelo efeito salting-out e LC-MS

Abstract

In this work a multiresidue method for the determination of three antiemetic drugs (ondansetron, metoclopramide and bromopride) in a sediment sample was developed and validated. Sediment samples were collected at 10 locations at the main campus of the Federal University of Santa Maria (UFSM), the first point being before the main UFSM stream enters the university and the last when the stream is no longer part of the university area. Quantification was performed with liquid chromatography coupled to mass spectrometry (LC-MS, quadrupole). Salting-out-assisted microextraction (SILLME) was the selected method for this study. The following extraction solvents were evaluated: acetone, acetonitrile, ethyl acetate, isopropyl alcohol, methanol, ethanol and a mixture of these in the proportion of 1:1 (v/v). The best recoveries were achieved using a mixture of ethyl acetate and acetone. The following salts were evaluated: anhydrous magnesium sulfate, magnesium sulfate heptahydrate, ammonium chloride, potassium phosphate, ammonium formate, sodium chloride, ammonium sulfate, anhydrous sodium sulfate, calcium carbonate, potassium hydrocarbon and hydrocarbon of calcium dihydrate. The use of anhydrous sodium sulfate provided the best results for all substances. The main factors more affecting the extraction of analytes were identified using the Plackett-Burman design containing 16 experiments and 3 center points. In this way, the sample mass, the proportion of the solvent mixture, the pH of the water, the amount of water, the mass of salt, the stirring time in both steps and the centrifugation time were optimized. Finally, the method was optimized using a central rotational composite design. The following conditions were selected: 0.5 g of sample, 5 mL of water at pH 9.5, 2.0 g of salt and a final step of stirring for 3.5 min, plus 5 min for centrifugation. The supernatant was removed, evaporated under flowing water at 40°C and resuspended in 1 mL of methanol acidified with 1% formic acid for analysis by LC-MS. All analytes were present at concentrations below the limits of quantification. The developed method was suitable for the three drugs and the method proved to be suitable for the detection and quantification of the three antiemetic drugs in complex matrices, such as sediment, allowing the detection of at least one of the investigated analytes.