Comprehensive toxicological screening of common drugs of abuse, new psychoactive substances and cannabinoids in blood using supported liquid extraction and liquid chromatography–quadrupole time-of-flight mass spectrometry.

This article focuses on the development and validation of a comprehensive toxicological screening method using high-resolution mass spectrometry (HRMS) with liquid chromatography–quadrupole time-of-flight mass spectrometry (LC–QTOF-MS) and All Ions data acquisition to detect over 200 drugs, including cannabinoids and new psychoactive substances (NPSs), in whole blood. The method addresses limitations of traditional immunoassay (IA) screening by improving analyte specificity, expanding the scope to include emerging drugs, and enabling retrospective data analysis. Supported liquid extraction (SLE) and dual positive/negative electrospray ionization (ESI) were optimized to reliably identify compounds at recommended cutoff concentrations for driving under the influence of drugs (DUID) investigations, including challenging analytes like 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH). Validation followed American National Standards Institute/Academy Standards Board (ANSI/ASB) guidelines, demonstrating acceptable limits of detection, reproducibility, matrix effects, carryover, and sample stability, while acknowledging some compromises inherent in universal extraction and non-targeted HRMS screening. The study highlights the utility of LC–QTOF-MS All Ions acquisition for broad, adaptable, and sensitive qualitative screening in forensic toxicology.