Advanced monitoring of psychoactive substances in hard candy using optimized ultrasound-assisted dispersive liquid-liquid microextraction and LC-MS/MS

Psychoactive substances, including narcotics and psychotropics, are frequently abused for recreational purposes, leading to addiction and severe health complications. Their deliberate contamination of foods also poses significant health risks. Effective monitoring and developing robust analytical methods to detect these substances are crucial. This study developed an ultrasound-assisted dispersive liquid-liquid microextraction (UA-DLLME) method that minimizes solvent and sample volume requirements, coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of eight psychoactive substances in hard candy. A Box-Behnken Design (BBD) evaluated three key factors influencing extraction efficiency: extraction solvent volume (X1; 1.5–2.5 mL), sodium chloride (NaCl) concentration (X2; 0–10 ), and pH (X3; 8–10). The response surface methodology (RSM) optimized analyte recovery, identifying optimal conditions as 1.5 mL ethyl acetate, 3.33 NaCl, and pH 8.14. Validation of the UA-DLLME-LC-MS/MS technique, performed according to international guidelines, demonstrated low limits of detection, reaching 0.004 µg g−1 (ketamine) and quantification (0.01 µg g−1) while providing high precision (coefficient of variation lower than 15 ), and accuracy (recoveries up to 106.50 ). This method successfully determined eight psychoactive substances in commercially available hard candy. © 2024 Elsevier Inc.