Journal of MASS SPECTROMETRY RESEARCH ARTICLE Investigation of sarin(Se) reactivity against human plasma proteins using liquid chromatography–tandem mass spectrometry Hamid Saeidian 1 | Seyed Esmaeil Hosseini 2,3 | Ali Amoozadeh 2 | Mohammad Taghi Naseri 3 | Mehran Babri 3 1 Department of Science, Payame Noor University (PNU), PO Box 19395‐4697 Tehran, Iran 2 Department of Chemistry, Semnan University, PO Box 35131‐19111 Semnan, Iran 3 Defense Chemical Research Lab (DCRL), PO Box 31585‐1461 Karaj, Iran Correspondence Hamid Saeidian, Department of Science, Payame Noor University (PNU), PO Box 19395‐4697, Tehran, Iran. Email: saeidian1980@gmail.com Abstract Electron ionization mass spectrum of sarin(Se) was interpreted in compare of sarin MS spectrum. Inhibition of butyrylcholinesterase of human plasma by sarin and sarin(Se) was determined spectrophotometrically using modified Ellman method. It appeared that after incubation with sarin and sarin(Se), cholinesterase inhibition were 93% and 83%, respectively. Sarin, sarin(Se), and sarin(Se)‐d 7 were spiked into a vial containing human plasma, and albumin adduct metabolites were identified using liquid chromatography–tandem mass spectrometry. The experiments show that these agents are attached to tyrosine on albumin in human blood. Corresponding deuterated adducts were used to confirm the proposed mechanisms for the formation of the fragments in mass spectrometry experiments. KEYWORDS acetylcholinesterase, adduct metabolites, liquid chromatography–tandem mass spectrometry, sarin, sarin(Se) 1 | INTRODUCTION Sarin, namely, O‐isopropyl methylphosphonofluoridate, is a well‐ known nerve agent, which was used for the first time during the Iran‐Iraq war and subsequently in terrorist attacks in Japan and recently was used in Syria conflict. 1 Such tragic events point to the great treat of chemical warfare agents, which unfortunately still remained. International community based on Chemical Weapons Convention (CWC) should work to eliminate the presence and use of chemical weapons. Millions of chemicals based on their potential risk and toxicity are listed in an annex to CWC in 3 distinct sched- ules (Scheduled chemicals). 2 Sarin belongs to the organophosphorus acetylcholinesterase inhibitors, which inhibit an enzyme called acetylcholinesterase (AChE). Inhibition of AChE results in overstimu- lation of cholinergic nerves, leading to sweating, miosis, respiratory paralysis, and finally death. 3,4 Synaptic AChE is not present in very large amounts in the human body. One AChE molecule can efficiently hydrolyze around 25 000 molecules of ACh per second; so blocking of this important enzyme quickly leads to fatal consequences. 5 Analysis of environmental samples such as water and soil can reveal the presence or absence of CWC‐related chemicals and/or their degradation products; but to assess if a potential victim was exposed, biomedical samples including blood and urine analysis is required. The main characteristics of organophosphorus nerve agents include high electrophilicity. They tend to accept electrons in chemical reactions, thus forming bonds with nucleophiles such as a serine hydroxyl group in AChE and a tyrosine hydroxyl in albumin. 6-8 Covalent adducts of nerve agents with blood proteins form suitable biomarkers, which have relatively longer lifetime and may exist in blood for up to several weeks' postexposure. Intact nerve agents and free metabolites are usually eliminated within the first 48 to 72 hours following exposure from the body. 8 Phosphorylated human albumin is potentially applicable as a biomarker and now is applicable to study of the effects of tabun, sarin, cyclosarin, VX, and organophosphorus pesticides. 9,10 On the other hand, compounds bearing selenium are toxic chemicals and should be avoided contact with them. 11,12 They are capable of forming covalent bond with biological molecules such as enzymes through their active sites. 13 Sarin(Se) is structurally similar Received: 3 September 2017 Revised: 24 October 2017 Accepted: 30 October 2017 DOI: 10.1002/jms.4045 138 Copyright © 2017 John Wiley & Sons, Ltd. J Mass Spectrom. 2018;53:138–145. wileyonlinelibrary.com/journal/jms