A green electrochemical sensor based on molecular imprinting for etoposide detection in environmental matrices

A semisynthetic form of podophyllotoxin, etoposide (ETO), is frequently used to manage multiple types of cancer, including lung, testicular, bladder, prostate, and gastric malignancies. Having been utilized in clinical settings for over twenty years, it is one of the most frequently prescribed anticancer agents globally. The primary cytotoxic mechanism of ETO involves the inhibition of topoisomerase II. In the present work, an innovative electrochemical detection platform utilizing MIP was successfully established to enable both highly selective and exceptionally sensitive determination of ETO in pharmaceutical injection forms and environmental specimens. An ETO-specific MIP sensor was fabricated through a photopolymerization process and immobilized onto a GCE, where AMPS served as the active monomer, and EGDMA functioned as the cross-linking agent. This study marks the first instance of a MIP-based electrochemical sensor designed explicitly for ETO identification. The AMPS-ETO@MIP/GCE sensor was subjected to electrochemical and morphological assessments through FTIR, SEM, CV, and EIS. An indirect measurement approach was employed using a 5.0 mM potassium ferricyanide/ferrocyanide system to ascertain the analytical detection range from 1.0 to 10.0 pM. The sensor demonstrated excellent sensitivity, reproducibility, and selectivity, enabling effective discrimination of ETO from structurally similar compounds while retaining reliable performance in complex matrices such as soil and tap water. Results from validation experiments in pharmaceutical matrices indicated superior recovery, supporting the sensor's practical effectiveness and stability. To further investigate the experimental results and better understand the nature of template–monomer interactions, a series of DFT calculations was performed. Binding energies were evaluated for ETO–AMPS complexes across varying template-to-monomer ratios.