In the present study, high throughput extraction of three highly polar ***** alkaloids, namely morphine, oxymorphone, and methylmorphine (codeine), was investigated using electromembrane extraction. Each alkaloid migrated from 24 mL of the sample solution through a supported liquid membrane containing di-(2-ethylhexyl) phosphate as the anionic carrier, dissolved in 2-nitrophenyl octyl ether, and into 10 μL of the acidic aqueous acceptor solution present inside the fiber lumen. Experimental design and response surface methodology were used for optimization of fundamental parameters affecting the extraction efficiencies of alkaloids including extraction voltage, extraction time, and pH of the donor and acceptor phases. After the microextraction process, the extracts were analyzed by high-performance liquid chromatography with ultraviolet detection. Under optimal conditions, alkaloids were extracted from various samples with enrichment factors in the range of 114–308 and 37–176 in water and urine samples, respectively. The proposed technique provided good linearity with correlation coefficient values higher than 0.9886. Limits of detection were in the range of 0.5–2.0 and 10.0–50.0 μg L−1 in water and urine samples, respectively. Also, limits of quantification were found in the range of 2.0–5.0 and 25.0–125.0 μg L−1 in water and urine samples, respectively. The maximum intra- and inter-day precisions (n = 3) were less than 9.5% and 12.4%, respectively.
