Spider diagram and Analytical GREEnness metric approach for assessing the greenness of quantitative 1H-NMR determination of lamotrigine: Taguchi method based optimization

Abstract An optimized eco-friendly quantitative proton nuclear magnetic resonance (1H NMR) method was developed for determination of lamotrigine. Taguchi method was utilized as a chemometric approach for the first time to optimize different NMR experimental parameters. The optimum acquisition conditions were found to be 128 number of scans, relaxation delay 1 s and pulse angle 90° using L16 (45) orthogonal array. The diagnostic doublet signal at 7.7 in the 1H NMR spectra was selected as quantitative peak for determination of lamotrigine. NMR spectra were obtained in dimethyl sulfoxide-d6 using phloroglucinol as internal standard. The content of lamotrigine was measured within the range of 5–50 μg/mL. The limits of detection (LOD) and limits of quantitation (LOQ) were 0.62 and 1.87 μg/mL respectively. The proposed method was successfully applied for determination of lamotrigine in tablet dosage form without interference from the commonly encountered excipients. The greenness of the developed method was assessed using Greenness Index with spider diagram, National Environmental Methods Index (NEMI), Analytical Eco-Scale and Analytical GREEnness metric approach (AGREE), it was found to be excellent green analytical method. By comparing with other reported methods, this study was the greenest one according to NEMI labeling and Analytical Eco-Scale score and the second one according to AGREE which ensure that quantitative NMR is a recent green analytical technique.