Antibiotics represent a class of pharmaceuticals used to treat bacterial infections. However, the ever-growing use of antibiotics in agriculture and human and veterinary medicine has led to great concern regarding the outbreak of microbe strains resistant to antimicrobial drugs. Azithromycin, clarithromycin, and erythromycin are macrolides, a group of molecules with a broad spectrum of antibiotic properties, included in the second EU watchlist of emerging pollutants which emphasizes the importance of understanding their occurrence, fate, and monitoring in aquatic environments. Thus, the aim of this study was to develop sensors based on nanostructured thin films deposited on ceramic substrates with gold interdigitated electrodes, to detect azithromycin, clarithromycin, and erythromycin in water matrices (mineral and river water). Impedance spectroscopy was employed as the transducing method for the devices’ electrical signal, producing multivariate datasets which were subsequently analyzed by principal component analysis (PCA). The PCA plots for mineral water demonstrated that ZnO- and TiO2-based sensors produced by DC magnetron sputtering either with 50% or 100% O2 in the sputtering chamber, were able to detect the three macrolides in concentrations between 10−15 M and 10−5 M. In river water, the PCA discrimination presented patterns and trends, between non-doped and doped, and sorting the different concentrations of azithromycin, clarithromycin, and erythromycin. Considering both matrices, by applying the e-tongue concept, sensitivity values of 4.8 ± 0.3, 4.6 ± 0.3, and 4.5 ± 0.3 per decade to azithromycin, clarithromycin, and erythromycin concentration, respectively, were achieved. In all cases, a resolution of 1 × 10−16 M was found near the 10−15 M concentration, the lowest antibiotic concentration measured.
