Quantification of 11 metabolites in rat urine after exposure to organophosphates.

Abstract

Background: The aim of the study was to develop a technique for quantitative determination of rat urine metabolites by HPLC-MS/MS, which can be used to search for biomarkers of acute intoxication with organophosphates (OPs).

Results: The content of metabolites in the urine of rats exposed to a single dose of paraoxon (POX1x); interval, twice daily administration of paraoxon (POX2x); exposure to 2-(o-cresyl)-4H-1, 3, 2-benzodioxaphosphorin-2-oxide and paraoxon (CBPOX) was investigated. New data were obtained on the content in the urine of intact rats as well as rats in 3 models of OP poisoning: 3-methylhistidine, threonine, creatine, creatinine, lactic acid, acetylcarnitine, inosine, hypoxanthine, adenine, 3-hydroxymethyl-butyrate and 2-hydroxymethyl-butyrate.

Conclusions: The proposed assay procedure is a simple and reliable tool for urine metabolomic studies. Within 1-3 days after OP exposure in all three models of acute intoxication, the concentration of metabolites in rat urine, with the exception of adenine, changes similarly and symmetrically, regardless of the method of poisoning modeling, in all three models of acute intoxication. Further studies are needed to determine the specificity and reliability of using urinary metabolite concentration changes as potential biomarkers of acute organophosphate intoxication.