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Carvedilol is a third generation non-selective beta-blocker and is marketed as a racemic mixture of (-)-(S) and (+)-(R) enantiomers (ADMINISTRATION, 2016; NARDOTTO et al., 2016). Methods that reduce organic solvent consumption and sample volume are important and attractive. Thus, the goal of this study was to develop and validate a method for the analysis of carvedilol enantiomers and lidocaine (internal standard, IS) in human plasma by salting out assisted liquid-liquid extraction (SALLE) and LC-MS /MS analysis. The identification of the factors that influence the efficiency of SALLE was performed using a 24-1 fractional factorial design with 4 factors. Subsequently, a central composite design (CCD) was used to evaluate the optimal extraction condition. The established SALLE extraction conditions were: 500 µL plasma, 50 µL carvedilol and IS, 1268 µL acetonitrile, 384 µL ammonium acetate solution 5 mol.L-1 and 10 min centrifugation.
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