Use of Box-Behnken design for the nuclear magnetic resonance study of molecular complex of anticonvulsant drug with N,N-dimethylformamide and its application in quantitative analysis

Abstract

The complex of pregabalin and N,N-dimethylformamide has been studied with magnetic resonance spectroscopy. NMR spectroscopy which is a well-acknowledged method in the field of chemistry from a larger view, but the utility exactly finds independent space in analytical chemistry. Taking this viewpoint, a precise, accurate and validated quantitative nuclear magnetic resonance (qNMR) method is proposed for an anti-convulsant and analgesic drug, Pregabalin. The instrumental optimization for the developed method was done using 400.13 MHz Bruker NMR spectrometer. Further, the experimental design approach was employed for the optimization of the experimental variables such as pregabalin concentration, acquisition time and number of scans using Box–Behnken design under response surface methodology. The analyte contents were evaluated at chemical shifts (δ) 0.835 ppm and 1.583 ppm, respectively. The final acquisition parameters (90° pulse angle, 4.0 s acquisition time, 10.0 s of relaxation delay time) prompted the analysis to be completed within 15 min. The method demonstrated good validation with impressive RSD values for intra-day assay 0.003 ― 0.17% and for inter-day assay 0.001 ― 0.04% with the recovery range of 99 ― 101%. The LOD and LOQ were found to be 0.12 mg mL−1 and 0.39 mg mL−1, respectively. The attained results of the qNMR method were then compared with the spectrophotometric method. Subsequently, the statistical treatment of the analytical data of the comparison revealed no significant difference between both the methods. The high precision value in case of qNMR is the additional advantage. Thus, the developed method is precise, accurate and a suitable tool for quantitative studies in bulk drug and its formulations.