Simultaneous LC-MS/MS screening of 222 drugs of abuse in eight solid food matrices using a unified QuEChERS-Based approach.

The intentional or inadvertent incorporation of drugs of abuse into food products has emerged as a significant forensic and public health concern, requiring analytical methods capable of reliable detection in complex food matrices. This study describes the development and validation of an LC-MS/MS method for the simultaneous determination of 222 drugs of abuse across diverse classes, including stimulants, benzodiazepines, opioids, cannabinoids, and emerging psychoactive substances. Eight representative solid food matrices (chocolate, cookie, coffee, brownie, snack, popcorn, jam, and tea) were analyzed using a unified QuEChERS-based extraction approach. Matrix-matched calibration curves were established and linearity evaluated based on a predefined acceptance criterion (R2 ≥ 0.98). LOQs ranged from ≤0.1 ng/g to above 10 ng/g depending on the analyte and matrix. LOQ and matrix effects were assessed across all matrices, and analytes not meeting quantitative criteria remained suitable for qualitative screening. The number of analytes suitable for quantitative determination varied by matrix, with the highest coverage observed in snack, chocolate, cookie, and brownie (121, 118, 108, and 108 analytes, respectively). The validated method provides a scalable platform for simultaneous screening of drugs of abuse in solid food matrices. However, application to authentic samples remains limited due to regulatory constraints.