Electrochemical determination of nitrazepam by switchable solvent based liquid-liquid microextraction combined with differential pulse voltammetry

In this article, a simple and efficient kind of homogeneous liquid-liquid microextraction based on an acid-base reaction using switchable-hydrophilicity solvents was proposed for the quantification of nitrazepam. Analyte is extracted into the N,N‑dipropylamine as an extraction solvent with the assistance of HCl and NaOH as pH adjustment reagents. Initially, a switchable solvent is added to the aqueous sample spiked with the analyte, which leads to the formation of a two phase mixture. Then, HCl is added drop by drop, until a clear and monophasic solution is obtained because of the switching of N,N‑dipropylamine into the hydrophilic form. Afterward, the separation of phases is achieved by addition of NaOH which results in switching back N,N‑dipropylamine to its primary hydrophobic form. Finally, after the evaporation of solvent, the extracted nitrazepam was analyzed by voltammetric methods. The influences of experimental factors on the extraction efficiency (organic solvent volume, pH of sample solution, extraction time, and salt addition) were investigated and optimized. Two linear ranges of 0.03-20 ng mL−1 and 20-450 ng mL−1 with the correlation coefficients of 0.996 and 0.998 were obtained from voltammetry measurements. The Limits of detection and quantification were obtained 9 ng L−1 and 0.03 ng mL−1 respectively. Also, the RSD% value of the method was calculated to be 7.4%. Finally, the proposed method was successfully applied for the determination of nitrazepam in human urine samples.