Adduct with a Tyrosine Residue

Binding of sarin and soman to a tyrosine residue present in blood has been observed by Black et al. (51) When sarin or soman was incubated with human plasma, phosphonylated tyrosine was observed by LC/MS after Pronase digestion, in addition to phosphonylated serine. The precise site of this residue has not yet been confirmed but it is associated with the albumin fraction. A phosphonylated tryptic peptide [/-PrO(CH3)P(0)]-Tyr-Thr-Lys, consistent with albumin, has been identified but this sequence is also present in other proteins. Before the advent of modem mass spectrometry, diisopropyl fluorophosphate was reported to bind 

After Pronase digestion of plasma, the analytes were concentrated on a C18 or C8 cartridge and analyzed by LC/MS/MS. The adducts have been detected in the blood of guinea pigs 24 h after being exposed to 0.5 LD50 doses of sarin and soman. It is not known if they are formed in cases of human exposure. 

The pulmonary agent phosgene was used extensively as a chemical weapon in WW I. Nowadays, it is an important intermediate for industrial production of insecticides, isocyanates, plastics, aniline dyes and resins, with an estimated yearly production of almost 1 billion pounds. Reliable diagnosis of exposure to phosgene, other than observation of the developing edema by means of chest roentgenology, is not available. 

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