We present a single-sensor, fluorescence-based platform using amphiphilic polymer-coated CdSe/ZnS quantum dots (PMA-QDs) for detection of isoniazid (INH), hydrazine (HZ), lactose (LAC), their mixtures, and commercial tablet formulations. The PMA-QDs exhibit distinct fluorescence quenching patterns upon interaction with each analyte, creating unique molecular fingerprints. Chemometric analysis with principal component analysis (PCA), linear discriminant analysis (LDA), and hierarchical clustering analysis (HCA) enabled accurate discrimination of individual compounds, mixtures, and tablet formulations, achieving 100% classification in leave-one-out cross-validation. The system showed high sensitivity to hydrazine, a toxic INH metabolite, detecting its formation under thermal stress and simulated in vitro metabolism. Furthermore, PMA-QDs distinguished between commercial INH tablet brands, demonstrating potential for quality control. Correlations between redox potentials and quenching efficiencies were observed, providing insight into the sensing mechanism. This versatile, multiplexed approach offers a practical strategy for drug screening, diagnostics, and metabolite monitoring in complex matrices.
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