Facile synthesis of 14C-nitrofurazone from 14C-urea

Authors: Singh, Anuradha; Smith, David

Submitted to: Journal of Labelled Compounds and Radiopharmaceuticals
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/6/2023
Publication Date: 11/8/2023
Citation: Singh, A., Smith, D.J. 2023. Facile synthesis of 14C-nitrofurazone from 14C-urea. Journal of Labelled Compounds and Radiopharmaceuticals. https://doi.org/10.1002/jlcr.4068.
DOI: https://doi.org/10.1002/jlcr.4068

Interpretive Summary: The antibiotic, nitrofurazone, is prohibited from use in food animals in most countries, including the US. The US and its trade partners monitor nitrofurazone residues in food products that are derived from animals. Semicarbazide (SEM) is used as a marker to identify whether the animals are treated/or untreated with nitrofurazone. But there are several incidences recognized where SEM was still detected even when no nitrofurazone was used. Therefore, it is necessary to identify a specific marker for nitrofurazone. For this purpose, metabolism studies with radiolabeled nitrofurazone were required. In this work a new synthetic method was developed to produce 14C-nitrofurazone in an economical manner and the material was used to conduct a metabolism study in poultry. The synthetic method will be used by academic, industrial, or governmental researchers to conduct studies on nitrofurazone metabolism and mechanisms of nitrofurazone biotransformation.

Technical Abstract: The veterinary drug nitrofurazone (5-nitro-2-furaldehyde semicarbazone) exhibits excellent antimicrobial properties but its application in food-producing animals is prohibited. The illegal use of nitrofurazone is regularly monitored by food regulatory agencies. Currently, semicarbazide (SEM) is used as a marker of nitrofurazone exposure. However, the use of SEM as a marker of nitrofurazone is under scrutiny after evidence of a high incidence of false positive tests. To overcome the current dilemma, it is necessary to identify a nitrofurazone-specific marker analyte which requires conducting nitrofurazone metabolism studies in food-producing animals. The use of carbon-14 labelled nitrofurazone would facilitate metabolism studies and structural elucidation of nitrofurazone metabolites of possible utility as a marker compound. In the present work, a synthetic method is described to procure radiolabeled -nitrofurazone that incorporates 14C- carbon at the semicarbazide moiety. The method installs 14C-carbon via employing readily available and more economically affordable 14C-urea compared to 14C-semicarbazide. To the best of our knowledge, there is no report on the synthesis of 5-nitro-2-furaldehyde 14C-semicarbazone from 14C-urea. The developed method involves monoamination of 14C-urea followed by a condensation reaction with 5-nitro-2-furaldehyde to produce 5-nitro-2-furaldehyde 14C-semicarbazone in 85% yield with greater than 98% radiochemical purity.