Permeably enclosed raw matrices direct analysis in real time mass spectrometry (PERM-DART-MS): a novel solution for the analysis of untreated samples.

Direct analysis of raw matrices by Direct Analysis in Real Time mass spectrometry (DART-MS) remains limited by logistical and operational challenges, including complex handling and positioning, risks of sample degradation, and contamination of the analytical instrument. The Permeably Enclosed Raw Matrices (PERM) approach, introduced here, provides a standardized and instrument-safe strategy in which samples are confined within a semipermeable enclosure, enabling practical and reproducible analysis while preventing particulate release and moderating thermal exposure. The method was evaluated using six chemically and physically diverse matrices of forensic, toxicological, and food relevance: seized tablets, seized powders, roasted coffee, human hair, plant material, and spiked whole human blood. Across all samples, PERM-DART-HRMS delivered S/N ratios spanning four orders of magnitude (4-44 k). The approach enabled the identification of both major and low-abundance constituents - including MDMA, MDA, diazepam, lorazepam, 3-MMC, 25I-NBOMe, N-MEC, caffeine, endogenous lipids such as cholesterol, and sesquiterpenes such as dehydrocostus lactone - without extraction, solubilization, or chromatographic separation. Comparative analysis against conventional DART-HRMS workflows demonstrated effective prevention of instrumental contamination and markedly improved operational reliability and efficiency. Altogether, PERM-DART-MS provides a unified, preparation-free platform for rapid chemical screening, offering a practical and reliable alternative for multidisciplinary applications in forensic, toxicological, and food science contexts.