Ultrasensitive and separation-free SERS detection of mitoxantrone in plasma via a charge-selective composite hydrogel

Therapeutic drug monitoring (TDM) of mitoxantrone (MIT) is essential for balancing efficacy and toxicity, yet current methods are limited by complex pretreatment, long turnaround times, and matrix interference. Herein, we developed a SERS sensor based on a pectin/AgNPs@CMC/CS/PAAM composite hydrogel for separation-free detection of cationic anticancer drugs in plasma. Fabricated via one-step UV photopolymerization, the hydrogel's dense network provides size-sieving to exclude plasma proteins, while abundant carboxyl groups confer a strong negative surface charge for selective electrostatic enrichment of positively charged drug molecules. This dual mechanism enhances specificity toward cationic analytes in complex matrices. Using MIT as a model, the sensor achieved 82.6%–101.7% recoveries in 10% plasma, a detection limit of 4.7 × 10 −10  M, and excellent reproducibility. Requiring only simple dilution, this platform offers a practical and ultrasensitive tool for TDM of cationic drugs in combination chemotherapy.