Deoxynivalenol (DON) sulfonates as major DON metabolites in rats: from identification to biomarker method development, validation and application

• Published in: Analytical and bioanalytical chemistry 2014-12, Vol.406 (30), p.7911-7924
• Main Authors: Schwartz-Zimmermann, Heidi E., Hametner, Christian, Nagl, Veronika, Slavik, Veronika, Moll, Wulf-Dieter, Berthiller, Franz
• Format: Article
• Language: English
• Subjects: Analysis; Analytical Chemistry; Animal species; Animals; Biochemistry; Biomarkers; Cereals; Characterization and Evaluation of Materials; Chemical properties; Chemistry; Chemistry and Materials Science; Chromatography, Liquid - methods; Deoxynivalenol; Deoxyribonucleotides; Feces; Feces - chemistry; Feces - microbiology; Food Science; Laboratory Medicine; Limit of Detection; Liquid chromatography; Male; Mass spectrometry; Mass spectroscopy; Metabolites; Methods; Monitoring/Environmental Analysis; Mycotoxins; Mycotoxins - analysis; Mycotoxins - metabolism; Mycotoxins - urine; Rats; Rats, Sprague-Dawley; Research Paper; Sulfonates; Sulfonic Acids - analysis; Sulfonic Acids - metabolism; Sulfonic Acids - urine; Tandem Mass Spectrometry - methods; Trichothecenes - analysis; Trichothecenes - metabolism; Trichothecenes - urine; Urine
• ISSN: 1618-2642; 1618-2650
• DOI: 10.1007/s00216-014-8252-3

Deoxynivalenol (DON) is a trichothecene mycotoxin regularly occurring in cereals. Rats are often used to study toxicokinetics of DON and related compounds, yet only about 30 % of the administered dose is typically recovered. Recently, it was reported that DON is partly metabolised to previously undetected DON- and deepoxy-DON (DOM) sulfonate in rats and tentative structures were proposed. The present work describes the production and characterisation of DON-, DOM- and DON-3-glucoside (D3G) sulfonates of three different series; the development and validation of liquid chromatography tandem mass spectrometry (LC-MS/MS)-based methods for determination of DON, DOM, D3G and their sulfonates in rat faeces and urine; and application of the methods to samples from a DON and D3G feeding trial with rats. In addition to previously produced DON sulfonates (DONS) 1, 2 and 3, D3G sulfonates 1, 2 and 3; and DOM sulfonates (DOMS) 2 and 3 were synthesised, purified and characterised. The developed methods showed apparent recoveries of all investigated compounds between 68 and 151 % in faeces and between 48 and 113 % in urine. The recovery of DON, D3G and their metabolites from faeces and urine of rats ( n  = 6) administered in a single dose of 2.0 mg/kg b.w. DON or the equimolar amount of D3G was 75 ± 9 % for the DON group and 68 ± 8 % for the D3G group. DON-, DOM- and D3G sulfonates excreted in faeces accounted for 48 and 47 % of the total amount of administered DON and D3G. Urinary excretion of sulfonates was