Background Amoxicillin (AMX), which is one of the β-lactam antibiotics used in the treatment of bacterial infections, is known to have a serious mechanism of resistance necessitating continuous monitoring of its level in pharmaceutical and serum samples. Results In this study, we presented selective, accurate, and precise square wave voltammetric method based on poly(4-amino-3-hydroxynaphthalene-1-sulfonic acid) modified glassy carbon electrode (poly(AHNSA/GCE)) for determination of amoxicillin

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... in four selected tablet brands. Appearance of a peak in the oxidative scan direction without a peak in the reductive direction of cyclic voltammograms of both bare GCE and poly(AHNSA/GCE) with four folds current and much reduced potential on the modified electrode showed catalytic property of the modifier towards oxidation of AMX. While cyclic voltammetric studies of effect of scan rate showed predominantly diffusion controlled oxidation of AMX with one electron participation, effect of pH revealed participation of protons and electrons in a 1:1 ratio. The square wave voltammetric peak current response of the modified electrode for AMX showed linear dependence on the concentration of the spiked standard AMX in the range 10–150 µmol L−1 with 9.9 nmol L−1 LOD. The AMX content of the studied tablet brands were found in the range 97.84–100.78% of the labeled value. Spike recovery results of 99.6–100.5%, and interference recovery results of 95.4–100.8% AMX in the presence of 50–200% of ampicillin and cloxicillin validated the applicability of the method for determination of amoxicillin in tablet formulation. Conclusion In contrast to the previously reported works on determination of amoxicillin, the present method showed an excellent performance making it a potential method for determination of amoxicillin in real samples including serum samples.