Quantitative determination and validation of topiramate and its tablet formulation by 1H-NMR spectroscopy. Issue 5 (18th January 2019) - Qin, Lingping
Abstract : An effective 1 H-qNMR method for the assay of topiramate has been established, which is significant for the quality control of topiramate. Abstract : In this study, a relatively simple and precise novel quantitative nuclear magnetic resonance spectrometry method to determine topiramate in a tablet formulation was developed on a 400 MHz NMR instrument. DMSO-d6 as the NMR solvent was selected. The signals of the methyl proton of topiramate appeared as four independent singlet peaks ( δ 1.47 ppm, δ 1.57 ppm, δ 1.34 ppm, and δ 1.29 ppm) with baseline separation. The δ 1.47 ppm (singlet) peak was selected for quantification. The δ 5.74 ppm (singlet) of 3, 5-dimethylpyrazole (DMP) was selected as the internal standard. The development and validation of this method were carried out as per International Conference on Harmonization (ICH) guidelines. Linearity ( R 2 = 0.9992) was observed between 0.05 and 0.85 mg mL −1 . The relative standard deviation for accuracy and precision was 2.0% or less. The limits of detection (LOD) and quantification (LOQ) were 0.04 and 0.16 mg mL −1, respectively. The robustness of the method was also investigated. The results showed that the method was accurate for the quantification of the topiramate tablet formulation, and was consistent with the method from the US Pharmacopoeia.