Solvent bar microextraction combined with HPLC-DAD and multivariate optimization for simultaneous determination of three antiarrhythmic drugs in human urine and plasma samples

A sensitive and simple microextraction approach was developed and validated to simultaneously determine three antiarrhythmic drugs, propranolol, diltiazem, and verapamil, in human urine and plasma samples, by combining solvent bar microextraction (SBME) with high-performance-liquid- chromatography diode-array detection. The optimization of SBME was initially investigated following a full factorial design (FFD) and subsequently by central composite design (CCD). With only 27 extraction tests using CCD, the optimum extraction conditions for selected drugs by SBME methodology were determined. The CCD allowed examining the linear, interaction, and quadratic influence of factors on drugs’ extraction efficiencies% (EE%), resulting in reduced size of SBME experiments. Under the optimal conditions, the calibration curves were linear in the ranges of 1.73–103 / 2.56–103 μg L−1 for propranolol, 2.32–103/ 2.83–103 μg L−1 for diltiazem, and 4.54–103/ 5.97–103 μg L−1 for verapamil at the respective urine/ plasma samples with reasonable linearity R2 > 0.978 in both matrixes. The ranged value of intra precision (RSD%, n = 5) for the selected drugs were from 1.30 to 5.66 and from 3.00 to 7.80 in urine and plasma samples, respectively. The limits of detection in urine/ plasma were 0.52/ 0.77 μg L−1, 0.69/ 0.84 μg L−1, 1.36/ 1.79 μg L−1 for propranolol, diltiazem, and verapamil, respectively. In comparison with referenced methods and based on the satisfactory results of applications, the proposed method can be considered a potential method for biopharmaceutical analysis of selected antiarrhythmic drugs in biological samples.