Simultaneous Measurement of Tabun, Sarin, Soman, Cyclosarin, VR, VX, and VM Adducts to Tyrosine in Blood Products by Isotope Dilution UHPLC-MS/MS

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• 作者：Brian S. Crow ; Brooke G. Pantazides ; Jennifer Qui帽ones-Gonz谩lez ; Joshua W. Garton ; Melissa D. Carter ; Jonas W. Perez ; Caroline M. Watson ; Dennis J. Tomcik ; Michael D. Crenshaw ; Bobby N. Brewer ; James R. Riches ; Sarah J. Stubbs ; Robert W. Read ; Ronald A. Evans ; Jerry D. Thomas ; Thomas A. Blake ; Rudolph C. Johnson
• 刊名：Analytical Chemistry
• 出版年：2014
• 出版时间：October 21, 2014
• 年：2014
• 卷：86
• 期：20
• 页码：10397-10405
• 全文大小：325K
• ISSN：1520-6882

文摘

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 渭L) 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鈭?0.0 ng/mL for GB鈥?and VR鈥揟yr and 0.250鈥?0.0 ng/mL for GA鈥? GD鈥? GF鈥? and VX/VM鈥揟yr (R² 鈮?0.995). Inter- and intra-assay precision had coefficients of variation of 鈮?7 and 鈮?0%, 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鈥? GB鈥? GD鈥? GF鈥? VR鈥? and VX/VM鈥揟yr, 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.