Abstract: The analysis of biomedicalsamples is one part of the verification programs of OPCW (Organization for theProhibition of Chemical Weapons), and the results would be used as evidence incase of allegations of chemical agents use. The organophosphorus nerve agentscould covalently conjugate with human butyrylcholinesterase (BChE), which isone of the most important biomarkers to verify an exposure to nerve agents. Inthis paper, the affinity SPE technology was employed as pretreatment method onthe case of the detection of serum samples. The difference of peptide massfingerprints between BChE and sarin-BChE was compared by matrix-assisted laserdesorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combinedwith trypsin digest, and the modified tryptic peptide by sarin (M+H⁺3 048.411 u) was found. The unmodified and modified fragments were alsoverified by tandem mass spectrometry, and the modified site could be attributedto Ser198. The method of verification of human plasma exposure to sarin can beused to track other organophosphorus agents successfully.