Semi-automated set-up for exhaustive micro-electromembrane extractions of basic drugs from biological fluids

Highlights: • Handling the microliter volumes of μ-EME operational solutions is semi-automated. • Extraction unit is connected to a syringe pump for withdrawal/infusion of μ-EME solutions. • Optimization of unique μ-EME variables enables exhaustive extraction of model analytes. • Basic drugs are exhaustively extracted from complex standards and urine/plasma samples. • This set-up represents the first step towards development of an automated μ-EME platform. - Abstract: Manual handling of microliter volumes of samples and reagents is usually prone to errors and may have direct consequence on the overall performance of microextraction process. Direct connection of a syringe pump and a disposable microextraction unit using flexible polymeric tubing was employed for semi-automated liquid handling in micro-electromembrane extraction (μ-EME). A three-phase μ-EME system was formed by consecutive withdrawal of microliter volumes of donor solution, free liquid membrane (FLM) and acceptor solution into the unit. Excellent repeatability and accuracy of the withdrawal sequence was achieved for solution volumes typically used in μ-EME (1–5 μL) as well as excellent correlation between the initially withdrawn and the finally collected solution volumes. μ-EMEs were initiated by application of d.c. electric potential to the terminal aqueous solutions and specific μ-EME parameters were optimized in order to ensure complete transfer of model analytes from donor to acceptor solution. Exhaustive μ-EMEs of three basic drugs, nortriptyline, papaverine and haloperidol, were achieved from 1.3 μL of acidified donor solution (10 mM HCl) across 2.5 μL of FLM (1-ethyl-2-nitrobenzene) into 1.3 μL of acidified acceptor solution (25 mM HCl) in 10 min at 150 V. The three drugs were also exhaustively extracted from salt- and protein-containing standard solutions, human urine and human plasma with extraction recoveries ranging from 79 to 102%. Resulting acceptor solutions were analysed by capillary electrophoresis with ultraviolet detection (CE-UV) and the μ-EME-CE-UV method was characterized by good linearity (coefficients of determination ≥ 0.992), high repeatability (RSD values ≤ 6.5%) and limits of detection ≤ 0.15 mg/L.