title: Procedures for Analysis of Dried Plasma Using Microsampling Devices to Detect Sulfur Mustard-Albumin Adducts for Verification of Poisoning.
abstract: Incorporation of the chemical warfare agent sulfur mustard (SM) produces a covalent adduct with human serum albumin (HSA) representing an established plasma biomarker of poisoning. Bioanalytical verification requires both plasma generation from whole blood and shipping to specialized laboratories following strict guidelines for complex packaging. These needs often push the infrastructural boundary in crisis regions and war zones. Therefore, we herein originally introduce different reliable bioanalytical procedures using filter paper as well as novel volumetric microsampling tools (Mitra devices and Noviplex DUO cards) to generate dried plasma samples not liable to the shipping constraints. In addition, the Noviplex device enables in-transit separation of plasma from whole blood without the need of a centrifuge. Plasma-loaded and dried devices were subjected to pronase treatment yielding the alkylated dipeptide hydroxyethylthioethyl-CysPro (HETE-CP) derived from the HSA-SM adduct that was detected by microbore liquid chromatography-electrospray ionization tandem-mass spectrometry (μLC-ESI MS/MS). For all devices, samples exposed to SM yielded excellent linearity (0.025-50 μM SM) and good precision (≤13%) and fulfilled forensic quality criteria for ion ratios of qualifying and quantifying product ions. Stability of the HSA-SM adduct in dried and liquid plasma is shown under conditions of three climatic zones (temperate climate, hot and dry climate, and hot and humid climate) for at least 9 days simulating the period of delayed sample shipping. Our results originally document that dried plasma is appropriate for storage and shipping at ambient temperature and that novel microsampling tools are of essential benefit when targeting the HSA-SM adduct for verification analysis.
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology , 80937 Munich, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: John
authors.affiliation: University of Applied Sciences and Arts Coburg , Department of Applied Sciences, Coburg, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: Willoh
authors.affiliation: University of Applied Sciences Weihenstephan-Triesdorf , Department of Biotechnology and Bioinformatics, Weihenstephan, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Hörmann
authors.affiliation: Department of Chemistry, Humboldt-Universität zu Berlin , Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Siegert
authors.affiliation: University of Applied Sciences and Arts Coburg , Department of Applied Sciences, Coburg, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Vondran
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology , 80937 Munich, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Thiermann
mesh_terms: D002619:Chemical Warfare Agents / Q000032:analysis* / Q000506:poisoning; D002853:Chromatography, Liquid / Q000295:instrumentation; D059788:Dried Blood Spot Testing / Q000295:instrumentation; D006801:Humans; D015394:Molecular Structure; D009151:Mustard Gas / Q000032:analysis* / Q000506:poisoning; D000075462:Serum Albumin, Human / Q000032:analysis*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation; D053719:Tandem Mass Spectrometry / Q000295:instrumentation
chemical_list: D002619:Chemical Warfare Agents; D009151:Mustard Gas; D000075462:Serum Albumin, Human