Rapid Measurement of Plasma Molecular-Targeted Drug Concentration with Boron-Doped Diamond Electrode

Compared to conventional cytotoxic anti-cancer drugs, molecular-targeted medications exhibit reduced toxicity. These drugs are administered to patients at fixed doses, without the need for adjustments based on biomedical indices such as body surface area. However, this therapeutic approach leads to considerable variability in plasma concentration among individuals, often resulting in significant adverse events that necessitate dosage reduction. Recent clinical studies have sought to quantify the correlation between drug concentration and clinical efficacy or toxicity. To enable personalized administration of molecular-targeted drugs, it is imperative to determine plasma concentrations directly at the clinical site. In recent years, advancements in medical engineering have yielded various portable or wearable biosensors capable of rapid on-site monitoring. Nonetheless, the widespread utilization of these devices has been hindered by insufficient evaluation of accuracy using clinical samples, variability between sensors, and the need for complex and costly fabrication processes. To overcome these challenges, we propose a straightforward approach utilizing untreated boron-doped diamond (BDD), an electrochemical material known for its sustainability. As a proof-of-concept, we selected pazopanib, a molecular-targeting anticancer drug recommended for monitoring. By employing a BDD plate chip measuring approximately 1 cm², our sensing system accurately detected pazopanib concentrations in rat plasma samples within the clinically relevant range. Furthermore, the response of the chip remained stable throughout 60 consecutive measurements, demonstrating its excellent repeatability. When we examined plasma samples collected from orally administered healthy rats and cancer patients using our system, the measured concentrations closely matched those obtained through liquid chromatography with mass spectrometry. Additionally, we evaluated the reproducibility of the BDD chips. Finally, we constructed a portable system featuring a palm-sized sensor housing a chip to facilitate practical implementation. This setup successfully determined drug concentrations from approximately 40 µL of whole blood obtained from dosed rats within a short turnaround time of approximately 10 minutes. By employing this "reusable" sensor-based approach, we can accelerate point-of-care drug monitoring, advance personalized medicine, and potentially reduce medical expenses.