Implementation of quality by design approach for optimization of the green voltammetric analysis of a brain doping agent (Piracetam) using a novel molecular imprinted polymeric sensor

Abstract

It is encouraging to note that in recent years there has been a growth of high-quality articles detailing molecular imprinted sensors for the detection of biomolecules, illicit narcotics, and explosives, paving the way for the technology's usage in forensic and medical diagnostics. Thus in this work, a molecularly imprinted polymeric sensor was fabricated, for the first time, for the sensitive and selective determination of a brain doping agent; Piracetam, using a pencil-graphite electrode. This sensor was created by the simple anodic electro-polymerization of o-phenylenediamine (o-PD) with Piracetam as the template. Then the sensor was activated by removing the template using a suitable solvent mixture. Because of Piracetam's lack of electro-activity, [Fe (CN)6]3−/4− has been used as an electrochemical probe that produces analytically relevant voltammetric signals by competing for the binding sites. Based on UV-spectrophotometric measurements, Job's approach confirmed the expected stoichiometric ratio between Piracetam and the chosen monomer. X-ray photoelectron spectroscopy and cyclic voltammetry techniques were used for the characterization of the fabricated sensors. Different factors affecting the electro-polymerization conditions as; the effect of scan rate, number of cycles, pH of electro-polymerization, and the incubation time for rebinding were studied and optimized using fractional factorial design, in which the predicted model fits well to the experimental data as proved by ANOVA results. The developed voltammetric platform was applied for the in-line quantification of Piracetam in its pure solutions, pharmaceutical dosage form, and spiked human plasma with high accuracy and selectivity without the interference of the co-formulated drug; Citicoline sodium and excipients. The proposed molecular imprinted sensor was very sensitive with a linearity range (1.00 × 10−13 − 1.00 × 10−12 M), with LOD down to 4.38 × 10−15 M. This method was statistically compared with the reported method, and no statistically significant difference was found. The proposed method was assessed for greenness quantitatively and qualitatively using the Green Analytical Procedure Index (GAPI) and Analytical GREEnness metric (AGREE) as new greenness assessment tools.