Application of a nucleophilic substitution reaction for spectrofluorimetric determination of aripiprazole in pharmaceutical dosage form and plasma matrix; greenness assessment

Abstract

Aripiprazole is an antipsychotic medicine used to treat a variety of mental disorders, including irritability linked with autism disorder in children. Herein, a green and highly sensitive spectrofluorimetric method was developed for the determination of aripiprazole in pharmaceutical dosage form and plasma matrix. The method based on the formation of a fluorescent adduct from the nucleophilic substitution reaction of 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-chloride) with aripiprazole, which can be detected at 542 nm following excitation at 481 nm. Factors that affect the development and fluorescence sensitivity of the reaction product were investigated and optimized. The reaction yielded the most optimal fluorescence responses when it was performed using 1.5 mL of 0.2 % w/v NBD-chloride, 1.5 mL of borate buffer pH 9, heating at 80 °C for 20 min, and ethanol as a diluting solvent. The method was validated as per ICH guidelines for analytical and bioanalytical procedures. Good linearity was established between the fluorescence responses of the reaction product and aripiprazole concentrations in the range of 100-1200 ng/mL with adequate accuracy and precision results. The applied method was very sensitive and selectively determined aripiprazole in pharmaceutical and plasma matrices with no interferences. Furthermore, the compliance of the proposed method with the principles of green analytical chemistry was evaluated in comparison with the reported method using analytical eco-scale and AGREE metrics. The outputs proved that the proposed method complied more with the principles of green analytical chemistry than the reported method.

Keywords: Aripiprazole; Fluorescence spectroscopy; Green analytical chemistry; NBD-Cl; Nucleophilic substitution reaction.