Evaluation of dried blood spot sampling for verification of exposure to chemical threat agents

• Published in: Forensic toxicology Vol. 43; no. 2; pp. 280 - 293
• Main Authors: Walker, Katie A., Rudd, Trinity K., Vignola, Justin N., McClymont, Thomas M., Roberts, Noah D., Laitipaya, Kevin, diTargiani, Robert C.
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.07.2025
• Subjects: Chemical Warfare Agents - analysis; Chromatography, Liquid; Dried Blood Spot Testing - instrumentation; Forensic Medicine; Forensic Science; Forensic Toxicology - methods; Humans; Medical Law; Medicinal Chemistry; Medicine; Medicine & Public Health; Original; Original Article; Pharmacology/Toxicology; Tandem Mass Spectrometry; Opioid; Liquid chromatography; Nerve agent; Mass spectrometry; Dried blood spot; Sulfur mustard
• ISSN: 1860-8965; 1860-8973
• DOI: 10.1007/s11419-025-00721-8

Purpose Exposure to chemical threat agents (CTAs), including nerve agents, the vesicating agent sulfur mustard, and opioids, remains a significant threat to warfighter and civilian populations. Definitive analytical methods to verify exposure to CTAs require shipping refrigerated or frozen biomedical samples to reference laboratories for analysis. Logistical and financial burdens arise as the transport of biomedical samples is subject to strict restrictions and complex packaging, which, if done incorrectly, can lead to sample deterioration. The use of dried blood spot (DBS) sampling could provide operational improvements for collecting, storing, and shipping important forensic samples. Therefore, this effort focuses on developing DBS techniques with Mitra® 30-µL volumetric absorptive microsampling (VAMS®) devices for use in CTA exposure verification. Methods VAMS® devices were loaded and dried with human whole blood that was exposed to the metabolites pinacolyl methylphosphonic acid (PMPA), ethyl methylphosphonic acid (EMPA), 1,1’sulfonylbis[2-(methylsulfinyl)ethane] (SBMSE), norfentanyl, norcarfentanil, norsufentanil, and norlofentanil. Following extraction from the VAMS® devices, metabolites were detected using liquid chromatography-tandem mass spectrometry (LC–MS/MS). The methods were validated for performance by assessing sensitivity, precision, accuracy, and recovery. Results These methods were sensitive to 1 ng/mL for SBMSE, 0.5 ng/mL for PMPA, EMPA, and norfentanyl; 0.1 ng/mL for norlofentanil, and 0.05 ng/mL for norsufentanil and norcarfentanil. All methods met acceptable precision and accuracy criteria with favorable recovery. Conclusions These results demonstrated the utility of VAMS® in stabilizing human whole blood and show promise as an improved collection method for verification of exposure to various CTAs.