Details:

Alternative Title:
Anal Chem
Publisher's site:
http://dx.doi.org/10.1021/ac502886c
Personal Author:
Crow, Brian S. ; Pantazides, Brooke G. ; Quiñones-González, Jennifer ; Garton, Joshua W. ; Carter, Melissa D. ; ... More +
Crow, Brian S. ; Pantazides, Brooke G. ; Quiñones-González, Jennifer ; Garton, Joshua W. ; Carter, Melissa D. ; Perez, Jonas W. ; Watson, Caroline M. ; Tomcik, Dennis J. ; Crenshaw, Michael D. ; Brewer, Bobby N. ; Riches, James R. ; Stubbs, Sarah J. ; Read, Robert W. ; Evans, Ronald A. ; Thomas, Jerry D. ; Blake, Thomas A. ; Johnson, Rudolph C. ; Less -
Description:
This work describes a new specific, sensitive, and rapid stable isotope dilution method for the simultaneous detection of the organophosphorus nerve agents (OPNAs) tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), VR, VX, and VM adducts to tyrosine (Tyr). Serum, plasma, and lysed whole blood samples (50 μL) were prepared by protein precipitation followed by digestion with Pronase. Specific Tyr adducts were isolated from the digest by a single solid phase extraction (SPE) step, and the analytes were separated by reversed-phase ultra high performance liquid chromatography (UHPLC) gradient elution in less than 2 min. Detection was performed on a triple quadrupole tandem mass spectrometer using time-triggered selected reaction monitoring (SRM) in positive electrospray ionization (ESI) mode. The calibration range was characterized from 0.100-50.0 ng/mL for GB- and VR-Tyr and 0.250-50.0 ng/mL for GA-, GD-, GF-, and VX/VM-Tyr (R(2) ≥ 0.995). Inter- and intra-assay precision had coefficients of variation of ≤17 and ≤10%, respectively, and the measured concentration accuracies of spiked samples were within 15% of the targeted value for multiple spiking levels. The limit of detection was calculated to be 0.097, 0.027, 0.018, 0.074, 0.023, and 0.083 ng/mL for GA-, GB-, GD-, GF-, VR-, and VX/VM-Tyr, respectively. A convenience set of 96 serum samples with no known nerve agent exposure was screened and revealed no baseline values or potential interferences. This method provides a simple and highly specific diagnostic tool that may extend the time postevent that a confirmation of nerve agent exposure can be made with confidence.
Subject:
[+]
Article
Blood Chemical Analysis
Chemical Warfare Agents
Chromatography, High Pressure Liquid
Humans
Organophosphorus Compounds
Organothiophosphorus Compounds
Reproducibility Of Results
Sarin
Soman
Spectrometry, Mass, Electrospray Ionization
Time Factors
Tyrosine

Source:
Anal Chem. 2014; 86(20):10397-10405.
Pubmed ID:
25286390
Pubmed Central ID:
PMC4515749
Document Type:
Journal Article ;
Funding:
JGZ8/Intramural CDC HHS/United States ;
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:0a5e2b0c30cefb119c5f48a4f9f331cd6dfcf1d7473c0628b373a37d8789e79c
File Type:

Supporting Files

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