Reduced drying times enable rapid paper spray analysis of whole blood for clinical toxicology

Abstract

Acute recreational drug toxicity is a common reason for presentation to the emergency department, but confirmatory toxicological testing is rarely available. Instead, clinicians rely on patient self-reporting and managing the clinical features. Paper spray ionisation-mass spectrometry enables direct analysis of dried blood spots; however, commonly observed ≥60 minutes drying time restricts clinical utility. This study investigated the impact of reduced drying intervals on analytical performance. Ten analytes were fortified into drug-free whole blood spots as pseudo-unknown samples and dried for 10, 20, 40 or 60 minutes alongside calibration curves. Analyses were performed by a Thermo Fisher Scientific VeriSpray™ Paper Spray Ion Source coupled to a Thermo Fisher Scientific Altis™ Plus Triple Quadrupole Mass Spectrometer. Orthogonal regression compared calibration curves across drying intervals, while pseudo-unknowns were evaluated for bias (%) and precision (% CV). All drying times demonstrated statistical agreement, with 95% CI for slopes and intercepts including 1 and 0 respectively. Precision was excellent (≤1%CV) and bias ranged between −9% and 30%. Ion ratios met acceptance criteria, ensuring reliable identification. Additionally, instrument performance was unaffected by shorter drying times. Whole blood spots dried for as little as 10 minutes yield confirmatory results equivalent to 60 minutes protocols. Reducing sample turnaround time to within 15 minutes of sample collection, this study provides a strong rationale for further translational research to support toxicology workflows in the emergency department and inform management of patients presenting with acute recreational drug toxicity.