Citation

John H, Siegert M, Eyer F, Worek F, Thiermann H, Kranawetvogl A. Toxicol. Lett. 2018; 294: 122-134.

Affiliation

Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany.

Copyright

(Copyright © 2018, Elsevier Publishing)

DOI

10.1016/j.toxlet.2018.05.023

PMID

29777832

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^®, 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 (ESO₂ET) leaving group, were simultaneously detected. Phosphorylated tyrosine residues (Tyr-DMP) derived from human serum albumin (HSA) as well as novel dipeptide-adducts containing the Cys³⁴ residue of HSA coupled to ESOET and ESO₂ET via a disulfide bond (ESOET-CysPro and ESO₂ET-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, ESO₂ET-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.

Copyright © 2018. Published by Elsevier B.V.

Language: en

Keywords

Albumin-adducts; cysteine disulfide-adducts; high-resolution mass spectrometry; organophosphorus pesticide; verification analysis