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A novel, entirely automated MicroNIR–chemometric platform was developed for the “lab-on-click” detection of illicit drugs in nonpretreated oral fluids, and a novel tool for the first-level test is proposed. Calibration of the method was achieved by collecting oral-fluid specimens from volunteers, and chemometric analysis was considered for the development of models for prediction for cocaine, amphetamine, and Δ9-tetrahydrocannabinol. In addition, a comprehensive model was optimized for the simultaneous prediction of positive–negative samples and the specific illicit drug used by abusers in a single “click”. The detection ability of the method was checked for true-positive and false-positive outcomes, and results were validated by a GC-MS reference official method. The MicroNIR–chemometric platform provided the simultaneous prediction of the three most frequently abused addictive drugs with the sensitivity and accuracy of the confirmatory analyses, offering the advantages of rapidity and simplicity and demonstrating that it is a promising tool for supporting public-health surveillance.

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