Development of Paper Spray Mass Spectrometry Cartridges with Solid Phase Extraction for Drug Screening Applications

The rise in overdoses, especially due to synthetic drugs like fentanyl has demonstrated a need for a rapid and simple drug detection method. This work describes the development and optimization of a paper spray mass spectrometry (PS-MS) with integrated solid-phase extraction (SPE) cartridges that can detect a wide range of drugs in plasma and whole blood The results can be obtained providing results in under five minutes with minimal sample preparation. The method is highly adaptable, allowing for rapid response to new emerging drugs. The initial focus on synthetic cannabinoids demonstrated sub-0.1 ng/mL detection limits for eight compounds in 100 µL of plasma. This work was expanded to screen thirty-five analytes from drug classes including fentanyl analogs, cathinones, benzodiazepines, and traditional illicit drugs. Validated according to SWGTOX guidelines, all drugs were detected in low ng/mL ranges. A streamlined data analysis method was also developed using a decision tree algorithm and an in-house library of nearly 200 compounds. This enabled retrospective analysis and detection of emerging drugs, such as 4F-MDMB-BINACA and brorphine, from previous samples. In a study of 400 authentic overdose plasma samples, 102 unique drugs were identified, mostly fentanyl-related. To further simplify the process, an "all-in-one" SPE cartridge was developed for whole blood, effectively pre-concentrating over 20 drugs of abuse. This device showed single and sub-ng/mL detection limits in 70 µL of blood. Samples were stable for 14 days, demonstrating the system’s potential for rapid, practical applications in forensic and clinical settings.