Abstract：
Nitrofurazone usage in food-producing animals is prohibited in most countries, including the United States. Regulatory agencies regularly monitor its use in domestic, export/import animals\' food products by measuring the semicarbazide (SEM) metabolite as a biomarker of nitrofurazone exposure. However, the use of SEM is controversial because it is also produced in food naturally and thus gives false positive results. A cyano-metabolite, 4-cyano-2-oxobutyraldehyde semicarbazone (COBS), is proposed as an alternate specific marker of nitrofurazone to distinguish nitrofurazone from treated or untreated animals. A synthetic method was developed to produce COBS via metallic hydrogenation of nitrofurazone. The product was isolated and characterized by one- and two-dimensional nuclear magnetic spectroscopy (NMR) experiments, Fourier-transform infrared spectroscopy (FT-IR), and mass spectrometry. The developed synthetic procedure was further extended to synthesize isotopically labeled 4-[13 C]-cyano-2-oxo- [2, 3, 4-13 C3 ]-butyraldehyde semicarbazone. Labeled COBS is useful as an internal standard for its quantification in food-producing animals. Thus, the developed method provides a possibility for its commercial synthesis to procure COBS. This is the first synthesis of the alternate specific marker metabolite of nitrofurazone for possible usage in regulatory analysis to solve a real-world problem.
摘要：
在大多数国家/地区，禁止在食用动物中使用硝基呋喃嗪，包括美国。监管机构定期监测其在国内的使用情况，出口/进口动物\'食品通过测量氨基脲（SEM）代谢物作为硝基呋喃酮暴露的生物标志物。然而,SEM的使用是有争议的，因为它也是在食品中自然产生的，因此会产生假阳性结果。一种氰基代谢物，4-氰基-2-氧代丁醛氨基脲（COBS），被提议作为硝基呋喃酮的替代特异性标记，以区分硝基呋喃酮与治疗或未治疗的动物。开发了一种通过硝基呋喃嗪金属加氢生产COBS的合成方法。分离产物，并通过一维和二维核磁光谱（NMR）实验进行表征，傅里叶变换红外光谱(FT-IR),和质谱。开发的合成程序进一步扩展到合成同位素标记的4-[13C]-氰基-2-氧代-[2,3,4-13C3]-丁醛氨基脲。标记的COBS可用作其在食品生产动物中定量的内标。因此，所开发的方法为其商业合成采购COBS提供了可能性。这是在调节分析中可能用于解决现实世界问题的硝基呋喃酮的替代特异性标记代谢物的首次合成。
