Rapid Quantitation of Non-chromophoric Vigabatrin and Gabapentin by a Validated qNMR Method in Bulk Drug and Marketed Formulations

Abstract

Background:: Vigabatrin and gabapentin, commonly used antiepileptic drugs in clinics, lack a UV active chromophore and, therefore, require cumbersome derivatization methods for analysis by HPLC using fluorescence detection. This study demonstrated the use of NMR for their quantitative determination in pure form and their pharmaceutical formulations. Objective:: To develop a validated qNMR method for non-chromophoric drugs Vigabatrin and Gabapentin. Methods:: The signal of methine proton of vigabatrin at 3.67 ppm relative to the signal of maleic acid at 6.17 ppm and the methylene signal of gabapentin at 2.88 ppm relative to the signal of caffeine at 7.75 ppm was used for qNMR. The developed method was validated with respect to linearity, limits of detection and quantitation, accuracy, precision, specificity and solution state stability. Results:: Linearity range and r2 were found to be from 2.66 to 42.11 mg/mL and 0.9999. The limit of detection and quantification were 0.0129 mg/mL and 0.0391 mg/mL, respectively, for vigabatrin. This method was found to be linear (0.9998) and specific within the gabapentin concentration range from 1.07 to 34.24 mg/mL of D2O. The limits of detection and quantification were 0.0248 mg/mL and 0.0751 mg/mL, respectively. Conclusion:: Both methods were highly precise, with a calculated RSD of 0.60 % and 0.76 %, respectively. The robustness of the methods was revealed by changing pre and post-processing NMR parameters. The developed methods provide a simple and straight approach for the absolute determination of gabapentin and vigabatrin in bulk drugs and their marketed formulations without any pre-procedures.