This work aimed at analyzing the performance of direct spectroscopic methods for the quantification of gabapentin (GABAp), given the lack of previous studies, in comparison with the more reviewed and complex derivatization techniques, discussing their susceptibility to the pharmaceutical formulations. All of the methods analyzed showed high selectivity for this pharmaceutical analyte, with recoveries close to 100%. Absorption spectroscopy without derivatization yielded better sensitivity and lower limits of detection and quantification of gabapentin in aqueous solution (AqSol method) when compared with other solvents, such as acidic solution or ethanol/water mixture. Derivatization with sodium hypochlorite presented the highest precision, whereas derivatization with vanillin exhibited the highest accuracy. The best method for GABAp quantification in terms of highest sensitivity, lowest limits of detection, and quantification, and also with good precision and accuracy, proved to be fluorescence with derivatization by 4-chloro-7-nitrobenzofurazan. The effect of the pharmaceutical formulation (nature of excipients) was tested for the most robust and sensitive methods, with and without derivatization, on capsules of five commercial brands. Recoveries in the range of 97.9–101.5% proved that there are no matrix interfering effects. Although not presenting the best performance in all the parameters evaluated, the AqSol method, due to its simplicity, proved to be suitable for the quantification of GABAp in capsules and tables containing the molecule as the active ingredient.
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