Graphitized Mesoporous Nanocomposites Enables Matrix-Free Soft Ionization for Multi-Class Drug Screening

The rapid proliferation of over a thousand new psychoactive substances (NPS) presents a growing challenge for global public health and forensic science, due to their structural diversity and widespread illicit use, which significantly complicate analytical detection. In response, a fundamentally reengineered ionization strategy is introduced that integrates mesoporous graphitic-zeolite nanoparticles (MGNs) with UV-activated photothermal nanomaterials into a next-generation surface-assisted laser desorption/ionization time-of-flight mass spectrometry (SALDI-TOF MS) platform. MGNs-hierarchically structured carbon-based semiconductors synthesized via chemical vapor deposition-exhibit an exceptionally high surface area (>900 m² g^-1), broadband light absorption, and efficient photothermal energy transfer. These properties collectively enhance desorption and ionization efficiency in the low m/z range (100-500), a region where small-molecule drug detection is often hindered by matrix interference and low signal fidelity. Compared to conventional organic matrices, the MGN-based system achieves a 95-fold improvement in signal-to-noise ratio and delivers quantification accuracies exceeding 90% for twelve representative compounds across seven drug classes, including structurally diverse NPS. Mechanistic investigations reveal that localized photothermal heating, in synergy with strong analyte adsorption within the mesoporous framework, accelerates soft ionization while suppressing background noise. This design enables rapid, reproducible, and interference-free detection-key to real-time diagnostics and screening applications.