Identification and Study of Biomarkers from Novichok-Inhibited Butyrylcholinesterase in Human Plasma

To identify biomarkers of ethyl (1-(diethylamino)ethylidene)phosphoramidofluoridate (A234)- or methyl (1-(diethylamino)ethylidene)phosphoramidofluoridate (A232)-inhibited butyrylcholinesterase (BChE), we investigated nonapeptide adducts containing the active site serine, which plays a key role in enzyme activity, using LC-MS/HRMS. Biomarkers were acquired as expected, and they exhibited a significant amount of fragment ions from the inhibiting agent itself, in contrast to the MS2 spectra of conventional nerve agents. These biomarkers had a higher abundance of [M+2H](2+) ions than [M+H](+) ions, making doubly charged ions more suitable for trace analysis.

Automated summary

Nonapeptide adducts containing the active site serine inhibited by ethyl or methyl phosphoramidofluoridate were studied using LC-MS/HRMS, revealing expected biomarkers with a higher abundance of doubly charged ions for trace analysis.