Greenness assessment profile of experimentally designed chromatographic method for the simultaneous analysis of ofloxacin and racecadotril in the presence of racecadotril impurities

Abstract

• Experimental design using face-centred composite design was utilized during method optimization to obtain the highest level of resolution with the fewest number of experimental trials for the determination of ofloxacin (OFLU) and racecadotril (RAC) in the presence of RAC impurities. • Experimental design is regarded as a more effective optimisation method since it takes into account the interaction among crucial elements impacting chromatographic separation. • The ecological impact of the presented technique was assessed utilizing the Analytical GREEnness Metric Approach and Software (AGREE) as an evaluation tool. Experimental design beats the conventional one variable at a time (OVAT) to improve the chromatographic separations with lowest consumption of resources and maximum acceptable results for the separated peaks. Experimental design using face-centred composite design was utilized during method optimization to obtain the highest level of resolution with the fewest number of experimental trials for the determination of ofloxacin (OFLU) and racecadotril (RAC) in the presence of RAC impurities. The two independent variables were the pH of solvent A (0.10% triethyl amine (pH 7 by orthophosphoric acid)) and its percentage in the mobile phase. RAC combined with OFLU is mainly used to treat diarrhoea in children. RAC has several impurities; among them is racecadotril impurity A (RAC-A) which was reported as a toxic impurity of RAC, additionally, RAC can be oxidized to racecadotril oxidative degradation product (RAC-Deg). Chromatographic separation was accomplished using Inertsil ODS column (150 mm, 4.6 mm, 5 μm) and isocratic elution using 0.10% triethyl amine (pH 7 by orthophosphoric acid) (solvent A): methanol (solvent B) (20:80 v/v) as a mobile phase at a flow rate of 1.00 mL/min and UV detection at 240 nm. Sharp, well-resolved peaks for RAC-Deg, RAC-A, OFLU and RAC were obtained with retention times of 1.70, 2.06, 7.11, and 8.98 min, respectively. Method validation was carried out according to ICH guidelines and linearity was achieved in the ranges of 2.00 – 20.00 and 3.00 – 25.00 µg/mL for RAC and OFLU, respectively. The ecological impact of the presented technique was assessed utilizing the Analytical GREEnness Metric Approach and Software (AGREE) as an evaluation tool. The new approach shown high accuracy, selectivity, precision, and environmental friendliness in determining the mentioned drugs in pharmaceutical formulations. It is suitable for routine analysis of the drugs in quality control laboratories.