Glutathione conjugates of the mercapturic acid pathway and guanine adduct as biomarkers of exposure to CEES, a sulfur mustard analog

Sulfur mustard (SM), a chemical warfare agent, is strong alkylating compound that readily reacts with numerous biomolecules. The goal of the present work was to define and validate new biomarkers exposure SM could be easily accessible in urine or plasma. Because investigations using are prohibited by Organization for Prohibition Chemical Weapons, we worked 2-chloroethyl ethyl sulfide (CEES), monofunctional analog SM. We developed an ultra-high-pressure liquid chromatography - tandem mass spectrometry approach (UHPLC-MS/MS) conjugate CEES glutathione two its metabolites, cysteine N-acetyl-cysteine conjugates. N7-guanine adduct (N7Gua-CEES) also targeted. After synthesizing specific biomarkers, solid phase extraction protocol UHPLC-MS/MS method isotopic dilution were optimized. able quantify N7Gua-CEES DNA HaCaT keratinocytes explants human skin exposed CEES. detected culture medium these models, together In contrast, not detected. then applied plasma from mice cutaneously All four markers Our results thus both analytical technique biological relevance new, quantifiable behaves very similarly SM, promising application this toxic interest.