An MIP-ECL sensor based on dummy-template imprinting and probe click-labeling for potential-resolved simultaneous detection of ruxolitinib and lenalidomide in therapeutic drug monitoring

A MIP-ECL sensor was developed for the dual-potential resolved simultaneous detection of RUX and LEN. • The combining dummy template imprinting with probes click-labeling enables simultaneous detection of signal-free analytes. • This strategy provides a new detection platform for therapeutic drug monitoring in combination therapy. Combination therapy is widely used in clinics to improve efficacy and reduce side effects by administering two or more drugs for personalized precise dosing. For the combination therapy of ruxolitinib (RUX) and lenalidomide (LEN) in primary myelofibrosis treatment, therapeutic drug monitoring (TDM) of both drugs in blood is required. This paper presents the development of a molecularly imprinted (MIP) electrochemiluminescence (ECL) sensor for the simultaneous detection of RUX and LEN. To address the challenge that neither RUX nor LEN generates ECL signals on electrodes, a dummy template molecule with terminal allyl groups, structurally similar to RUX, was designed to copolymerize with LEN for the preparation of the MIP film. A novel strategy based on dummy template competitive adsorption and photo-initiated click reactions was developed for simultaneous determination of RUX and LEN. It relies on the competitive adsorption between RUX and its dummy template on MIP, followed by click labeling of two ECL probes onto the dummy template and LEN, with detection of RUX and LEN achieved by recording the cathodic and anodic ECL signals, respectively. The MIP-ECL sensor exhibits a detection range of 5 to 5000 ng/mL for both RUX and LEN, with detection limits of 0.11 ng/mL and 0.49 ng/mL, respectively. The sensor was successfully applied to the analysis of human serum samples. It not only provides a novel approach for the detection of multiple targets without responding signals using MIP, but also offers a more sensitive and convenient technical platform for TDM. An MIP-ECL sensor combining dummy-template imprinting with probe click-labeling was developed for the potential-resolved simultaneous detection of ruxolitinib and lenalidomide. This strategy overcomes the challenge of simultaneously detecting signal-free analytes and amplifies detection signals, improving sensitivity with LODs of 0.11 ng/mL for ruxolitinib and 0.49 ng/mL for lenalidomide. Download: Download high-res image (193KB) Download: Download full-size image