Simultaneous and Selective Detection of Etoposide and Methotrexate With Single Electrochemical Sensors for Therapeutic Drug Monitoring

Etoposide (ETO) and methotrexate (MTX) are widely used chemotherapy drugs in cancer treatment, targeting specific cellular processes crucial for DNA replication and cell division. Despite their efficacy, both drugs have significant adverse toxic effects due to the narrow therapeutic window, which can result in either overexposure or insufficient exposure. Therefore, providing therapeutic drug monitoring (TDM) is crucial to optimize pharmacotherapy outcomes to provide optimal dosage adjustment, and minimize adverse effects with personalized medicine and therapy. Conventional cytotoxic chemotherapies involve the combination of multiple antineoplastic drugs. Therefore, when developing sensors for TDM, it is important to account for the potential interactions between different drugs when they are simultaneously present in the blood of patients. However, the electrochemical interaction between ETO and MTX has not been studied in multiplexed concentration monitoring. Therefore, our study aims to investigate their oxidation mechanism during simultaneous detection on the same sensor. We actually succeeded in demonstrating not only the simultaneous detections of the two drugs but also their mutual interference due to their oxidative cross-reactivity. To that aim, the reaction mechanisms between ETO and MTX during their interaction on our sensor are presented in detail in this letter. A deep understanding of such an interaction is clearly crucial to calibrate the sensor in order to provide accurate and reliable detection of the two anticancer compounds.