title: Generation of semicarbazide from natural azine development in foods, followed by reaction with urea compounds.
abstract: This paper proposes a mechanism to explain the trace levels of natural semicarbazide occasionally observed in foods. The analytical derivative of semicarbazide, 2-nitrobenzaldehyde semicarbazone, is often measured as a metabolite marker to detect the widely banned antibiotic nitrofurazone. However, this marker is not specific as semicarbazide may be present in foods for several reasons other than exposure to nitrofurazone. In some cases, an entirely natural origin of semicarbazide is suspected, although up until now there was no explanation about how semicarbazide could occur naturally. In this work, semicarbazide is proposed as being generated from natural food compounds via an azine intermediate. Hydrazine, in the form of azines or hydrazones, may be generated in dilute aqueous solution from the natural food compounds ammonia, hydrogen peroxide and acetone, following known oxidation chemistry. When this mixture was prepared in the presence of ureas such as allantoin, urea, biuret or hydroxyurea, and then analysed by the standard method for the determination of semicarbazide, 2-nitrobenzaldehyde semicarbazone was detected. 2-Nitrobenzaldehyde aldazine was also found, and it may be a general marker for azines in foods. This proposal, that azine formation is central to semicarbazide development, provides a convergence of the published mechanisms for semicarbazide. The reaction starts with hydrogen peroxide, peracetic acid, atmospheric oxygen or hypochlorite; generates hydrazine either by an oxaziridine intermediate or via the chlorination of ammonia; and then either route may converge on azine formation, followed by reaction with a urea compound. Additionally, carbamate ion may speculatively generate semicarbazide by reaction with hydrazine, which might be a significant route in the case of the hypochlorite treatment of foods or food contact surfaces. Significantly, detection of 2-nitrobenzaldehyde semicarbazone may be somewhat artefactual because semicarbazide can form during the acid conditions of analysis, which can free hydrazine in the presence of urea compounds.
authors.affiliation: a Fonterra Research and Development Centre , Private Bag 11029, Palmerston North 4442 , New Zealand.
authors.forename: Grant A
authors.initials: GA
authors.lastname: Abernethy
mesh_terms: D005503:Food Additives / Q000737:chemistry*; D005504:Food Analysis; D006834:Hydrazines / Q000737:chemistry*; D006868:Hydrolysis; D015394:Molecular Structure; D012663:Semicarbazides / Q000138:chemical synthesis* / Q000737:chemistry; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry*
chemical_list: D005503:Food Additives; D006834:Hydrazines; D012663:Semicarbazides; C029424:hydrazine; C010059:carbamylhydrazine; D014508:Urea
keywords: allantoin; azine; milk; natural hydrazine formation; nitrofurazone; semicarbazide