Chlorine is a public health concern and potential threat due to its high reactivity, ease and scale of production, widespread industrial use, bulk transportation, massive stockpiles, and history as a chemical weapon. This work describes a new, sensitive, and rapid stable isotope dilution method for the retrospective detection and quantitation of two chlorine adducts. The biomarkers 3-chlorotyrosine (Cl-Tyr) and 3,5-dichlorotyrosine (Cl2-Tyr) were isolated from the pronase digest of chlorine exposed whole blood, serum, or plasma by solid phase extraction (SPE), separated by reversed-phase HPLC, and detected by tandem mass spectrometry (MS/MS). The calibration range is 2.50–1000 ng/ml (R2 ≥ 0.998) with a lowest reportable limit (LRL) of 2.50 ng/mL for both analytes, an accuracy of ≥ 93%, and an LOD of 0.443 ng/mL for Cl-Tyr and 0.396 ng/mL for Cl2-Tyr. Inter- and intra-day precision of quality control samples had coefficients of variation of ≤ 10% and ≤ 7.0%, respectively. Blood and serum samples from 200 healthy individuals and 175 individuals with chronic inflammatory disease were analyzed using this method to assess background levels of chlorinated tyrosine adducts. Results from patients with no known inflammatory disease history (healthy) showed baseline levels of

No abstract

Biomedical samples may be used to determine human exposure to nerve agents through the analysis of specific biomarkers. Samples received may include serum, plasma, whole blood, lysed blood and, due to the toxicity of these compounds, postmortem blood. To quantitate metabolites resulting from exposure to sarin (GB), soman (GD), cyclosarin (GF), VX and VR, these blood matrices were evaluated individually for precision, accuracy, sensitivity and specificity. Accuracies for these metabolites ranged from 100 to 113% with coefficients of variation ranging from 2.31 to 13.5% across a reportable range of 1-100 ng/mL meeting FDA recommended guidelines for bioanalytical methods in all five matrices. Limits of detection were calculated to be 0.09-0.043 ng/mL, and no interferences were detected in unexposed matrix samples. The use of serum calibrators was also determined to be a suitable alternative to matrix-matched calibrators. Finally, to provide a comparative value between whole blood and plasma, the ratio of the five nerve agent metabolites measured in whole blood versus plasma was determined. Analysis of individual whole blood samples (n = 40), fortified with nerve agent metabolites across the reportable range, resulted in average nerve agent metabolite blood to plasma ratios ranging from 0.53 to 0.56. This study demonstrates the accurate and precise quantitation of nerve agent metabolites in serum, plasma, whole blood, lysed blood and postmortem blood. It also provides a comparative value between whole blood and plasma samples, which can assist epidemiologists and physicians with interpretation of test results from blood specimens obtained under variable conditions.

Effects. -The title reaction yielding the corresponding N-oxides is investigated. An excellent correlation with Hammett's sigma values is observed. -(WINKELJOHN, W. R.; VASQUEZ, P. C.; STREKOWSKI, L.; BAUMSTARK*, A. L.; Tetrahedron Lett. 45 (2004) 45, 8295-8297; Dep. Chem., Ga. State Univ., Atlanta, GA 30303, USA; Eng.) -Mais 07-129

No abstract