Electrically stimulated liquid phase microextraction combined with differential pulse voltammetry: a new and efficient design for in situ determination of clozapine from complicated matrices

In this work, for the first time, a new, simple, low-cost and efficient design was presented for in situ determination of clozapine (CLZ) from human plasma samples by combination of electromembrane extraction (EME) with differential pulse voltammetry (DPV). The charged target analyte was extracted by applying a 200 V d.c. electrical potential from an acidic sample solution, through the supported liquid membrane (SLM) into an acidic acceptor solution, which was located in the lumen of a porous hollow fiber. 2-Nitrophenyl octyl ether (NPOE) was impregnated into the pores of the hollow fiber and used as the SLM. Three microelectrodes, an Ag/AgCl, a platinum wire, and a graphite pencil lead as the reference, counter and working electrodes, respectively, were fixed by passing through a septum and located into a pipette tip connected to the upper end of the hollow fiber for electrochemical analysis of CLZ. Central composite design and response surface methodology were used to optimize the main parameters influencing the extraction efficiency and analytical response (current) including pH of donor and acceptor phases, extraction time and electrical potential difference. Under the optimized conditions, the proposed method showed a wide linear range of 3–1500 ng mL −1 with a determination coefficient higher than 0.993. Extraction recovery of 42% was achieved which corresponded to a preconcentration factor of 114. Limits of detection and quantification of 0.9 ng mL −1 and 3.0 ng mL −1 were obtained, respectively. The intra- and inter-day precisions (RSD%, n = 3) were less than 3.5% and 6.7%, respectively. Finally, the proposed method was successfully applied for determination of CLZ from some human plasma samples.