@article{ref1,
title="Novel cysteine- and albumin-adduct biomarkers to prove human poisoning with the pesticide oxydemeton-S-methyl",
journal="Toxicology letters",
year="2018",
author="John, Harald and Siegert, Markus and Eyer, Florian and Worek, Franz and Thiermann, Horst and Kranawetvogl, Andreas",
volume="294",
number="",
pages="122-134",
abstract="We herein report on the forensic analysis of plasma samples to prove human poisoning with oxydemeton-S-methyl (ODM), S-(2-(ethylsulfinyl)ethyl)-O,O-dimethyl phosphorothioate. This organophosphorus pesticide is the active ingredient of Metasystox<sup>®</sup>, that was swallowed by a 77-year-old woman to commit suicide. ODM belongs to the class of dimethyl phosphoryl (DMP) pesticides, contains a 2-(ethylsulfinyl)ethanethiol (ESOET) leaving group and undergoes adduct formation with endogenous molecules as elaborated herein with human serum exposed to pesticides in vitro. A novel bioanalytical micro liquid-chromatography-electrospray ionization tandem high-resolution mass spectrometry method (µLC-ESI MS/HR MS) was developed to target multiple biomarkers of exposure. Following pronase-catalyzed proteolysis of patient plasma and subsequent ultrafiltration, the filtrate was analyzed. Diverse reaction products of ODM as well as of its oxidized biotransformation product demeton-S-methyl sulfone (DSMS), that possesses a 2-(ethylsulfonyl)ethanethiol (ESO<sub>2</sub>ET) leaving group, were simultaneously detected. Phosphorylated tyrosine residues (Tyr-DMP) derived from human serum albumin (HSA) as well as novel dipeptide-adducts containing the Cys<sup>34</sup> residue of HSA coupled to ESOET and ESO<sub>2</sub>ET via a disulfide bond (ESOET-CysPro and ESO<sub>2</sub>ET-CysPro) were found. In addition, a related disulfide-product was detected comprising the single amino acid cysteine and ESOET (ESOET-Cys). Whereas Tyr-DMP only proved the intake of any DMP pesticide in general, its simultaneous detection with ESOET-CysPro, ESO<sub>2</sub>ET-CysPro and ESOET-Cys allowed unambiguous identification of the ingested pesticide. Therefore, the novel biomarkers and the method developed expand the possibilities of forensic investigations of ODM poisoning.<br><br>Copyright © 2018. Published by Elsevier B.V.<p /> <p>Language: en</p>",
language="en",
issn="0378-4274",
doi="10.1016/j.toxlet.2018.05.023",
url="http://dx.doi.org/10.1016/j.toxlet.2018.05.023"
}