A novel application of deep eutectic solvents in quantitative nuclear magnetic resonance using grey relational analysis for multi-response optimization

摘要

Developing new green solvents is one of the key subjects in Green Chemistry. Deep eutectic solvents (DES), as a new green class of tailor-made solvents, have attracted increasing attention in many areas of science because of their unique properties such as availability, low cost, biodegradability and environmental friendliness of its components. DES have been applied in many fields of chemical processing however, the full potential of these solvents is still unexplored. With an in-depth understanding of DES common properties, a novel application of DES was proposed as solvent for quantitative nuclear magnetic resonance (qNMR). In this study, an acidic DES of choline chloride and trifluoroacetic acid (TFA) at 1:3 M ratio diluted with deuterium oxide (50%) was used as qNMR solvent for simultaneous determination of Tinidazole (TZ) and Norfloxacin (NF) in pharmaceutical dosage form. This article focuses on grey relational analysis (GRA)-based Taguchi method for multi-response optimization of NMR processing parameters for the resultant of NF and TZ integral values ratios to internal standard (IS) and their coupling constant. This approach is adopted to transfer multi-response into a single response of grey relational grade (GRG). The optimal NMR processing parameters were found to be 148 number of scans, 20 s relaxation delay and 30 degrees pulse angle. Based on the analysis of variance, number of scans was found to have the highest impact of 36.73%. Confirmation experiments conducted using the optimal parameters indicated an improvement of 56.34% in GRG. The qNMR determination of studied drugs depends on measuring the integral values ratios of the diagnostic triplet signals at 0.0025 and 0.25 ppm in H-1-NMR spectra as quantitative signals of TZ and NF, respectively to IS (Formic acid) singlet signal at 6.8 ppm. Calibration curves were created by plotting these integral ratios versus the concentration for each drug that displayed good linear relationships in the concentration ranges of 0.3-12.0 and 0.2-8.0 mg mL(-1) for TZ and NF, respectively.