In this work a new synthetic hydrogel was applied to the synthesis of gold nanoparticles (GNPs). Poly(styrene-alt-maleic acid) pH-sensitive hydrogel, bearing negatively charged COO− groups, was used for this purpose. There was no need for the additional reducing agent and surfactant for the synthesis of GNPs. The optimum conditions for synthesis of the GNPs were obtained by studying the effects of pH and concentration of hydrogel. The structure, size and morphology of the synthesized GNPs were investigated by UV–vis spectra and transmission electron micrograph (TEM), respectively. In addition, the interactions between synthesized GNPs with several drugs such as acetaminophen (ACET), ascorbic acid (AA) and folic acid (FA) were studied. The results showed that the synthesized GNPs can be used as a new and highly efficient spectrophotometric sensor for the selective recognition and monitoring of three drugs in real samples such as serum samples. The sensitivity and selectivity of GNPs toward other drugs as potential interferents were also studied. The linear ranges for the spectrophotometric determination of ACET, AA and FA were calculated as well. Limit of detection (calculated as 3 times of standard deviation of blank) were obtained as 1.8 × 10−6 M, 2.7 × 10−7 M, 2 × 10−6 M for ACET, AA and FA, respectively. The proposed method was successfully used to the determination of ACET, AA and FA in various serum samples.
