Real-Time Detection of Cardiotoxic Anticancer Drug by Diamond Microsensors in the Skin and Combined Monitoring of Electrocardiogram in Live Rats

In vivo real-time detection of pharmacokinetics of systemically administrated drugs in microenvironments advance pharmacology and clinical medicine. Here, we describe an analytical platform targeting dermal interstitial fluid with a needle-type microsensor of a boron-doped diamond (BDD) electrode. A test analyte was doxorubicin, an anticancer drug that induces acute cardiotoxicity. Upon intravenous bolus injection of doxorubicin to anesthetized rats, a BDD microsensor inserted into the dermis unexpectedly detected two sequential phases of the concentration change: a first component elicited in several minutes with fast kinetics and a sharp peak, and a subsequent second response maximized from 15 min to 1 h with slow kinetics. Furthermore, the BDD microsensing system was combined with electrocardiography, visualizing a relationship between doxorubicin's behavior in the skin and induction of QT-interval prolongation. Our approach may clarify detailed local pharmacokinetics and its correlation with pharmacodynamics and provide a prototype wearable device for next-generation drug monitoring.