Paper spray mass spectrometry for rapid toxicology targeted screening of emergency department samples: a research study.

Acute recreational drug toxicity (ARDT) is a frequent cause of emergency department (ED) presentations, yet comprehensive toxicological testing by chromatographic techniques is rarely conducted due to limited availability and resource-intensive workflows. Consequently, initial clinical decisions are made without analytical confirmation. Paper spray-mass spectrometry (PS-MS) may offer an alternative approach for targeted clinical toxicology screening owing to its rapid and simplified analysis of biological samples. Serum donor samples from patients presenting to the ED with suspected ARDT were analyzed using PS-MS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for method comparison. Targeted screening and quantitative performance were evaluated using pooled diagnostic metrics, orthogonal regression, per-analyte % bias and Bland-Altman analyses. PS-MS was subsequently applied to a larger screening-only cohort to assess analytical performance, detection frequency, and concentration distributions across a clinically relevant drug panel. Across 114 research samples, PS-MS demonstrated high targeted screening performance, with a pooled sensitivity of 82.7%, specificity and positive predictive value of 100%, and negative predictive value of 98.2%. Quantitative comparison showed strong correlation between methods, with proportional bias at higher concentrations and no single analyte influencing the agreement metrics. In the screening-only cohort (n = 99), PS-MS detected and quantified a broad range of analytes, including evidence of polydrug use. Several low-frequency analytes were not observed within the analyzed serum donor sample cohort. PS-MS may provide a fast and specific targeted screening approach for ARDT in ED samples, delivering analytically informative toxicological data. While not a replacement for confirmatory testing or a validated in vitro diagnostic assay, this research study into PS-MS represents a valuable complementary tool to support downstream confirmatory testing.