Desirability function approach for the optimization of an in‐syringe ultrasound‐assisted emulsification‐microextraction method for the simultaneous determination of amlodipine and nifedipine in plasma samples

In the present study, an in‐syringe ultrasound‐assisted emulsification‐microextraction using a low‐density organic solvent was developed for simultaneous extraction and pre‐concentration of amlodipine besylate and nifedipine from plasma samples. The extracts were analyzed by high‐performance liquid chromatography with UV detection. Central composite design combined with desirability function was applied to find out the optimal experimental conditions providing the highest global extraction efficiency. The optimal conditions identified were volume of the extracting solvent 45 μL, ionic strength 18.95% w/v, sonication time 2.58 min, and centrifugation time 3 min. Under the optimal conditions, the proposed method was evaluated, and applied to the analysis of amlodipine besylate and nifedipine in plasma samples. The validation results of the method indicated a wide linear range (2–1200 ng/mL) with a good linearity (r² >0.9991) and low detection limits (0.17 ng/mL for amlodipine besylate and 0.15 ng/mL for nifedipine) with RSD less than 5.2% for both components, both in intra‐ and inter‐day precision studies. The applicability of the proposed in‐syringe ultrasound‐assisted emulsification‐microextraction coupled to high‐performance liquid chromatography with UV detection method was demonstrated by analyzing the drugs in spiked plasma samples.