Ochratoxin A (OTA) is a nephrotoxic mycotoxin with nephrocarcinogenic potential found in a broad spectrum of food commodities. The mode of action of this compound, as well as its metabolism, is still not fully understood. To determine whether the conjugation of OTA with glutathione plays an important role in human OTA metabolism, an ochratoxin-glutathione conjugate (OTB-GSH), as well as the corresponding urinary metabolite ochratoxin-N-acetyl-l-cysteine (OTB-NAC), were synthesized and their structures confirmed by NMR spectroscopy. By means of synthesized stable isotope-labeled d₅-OTB-GSH and d₅-OTB-NAC references, a sensitive HPLC-MS/MS method has been developed and applied for the screening of human urine samples. OTB-NAC could be detected in 11 of the analyzed 18 urine samples and was quantified in 5 urine samples in the range between 0.023 and 0.176 ng mg⁻¹ creatinine. OTB-GSH has not been detected in the urine samples. In OTB-NAC positive samples, this metabolite contributed to a comparable concentration range to the total OTA excretion as the parent compound. This is the first direct analysis of an OTA phase 2 metabolite in humans.

中文翻译：

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曲毒素-N-乙酰基-L-半胱氨酸的鉴定是一种新的曲毒素A代谢物和人类尿液中潜在的生物标志物。

ch曲霉毒素A（OTA）是一种在多种食品中发现的具有肾致癌潜力的肾毒性霉菌毒素。该化合物的作用方式及其新陈代谢尚未得到充分了解。为了确定OTA与谷胱甘肽的结合在人OTA代谢中是否起重要作用，,曲霉毒素-谷胱甘肽共轭物（OTB-GSH）以及相应的尿代谢产物ra曲霉毒素-N-乙酰基-L-半胱氨酸（OTB-NAC） ，合成了它们，并通过NMR光谱确认了它们的结构。通过合成的稳定同位素标记的d ₅ -OTB-GSH和d ₅-OTB-NAC参考文献已开发出一种灵敏的HPLC-MS / MS方法，并已用于筛查人尿液样品。可以在分析的18个尿液样本中的11个中检测到OTB-NAC，并在5个尿液样本中对OTB-NAC进行定量，其范围为0.023至0.176 ng mg ^-1肌酐。尿液样本中未检测到OTB-GSH。在OTB-NAC阳性样品中，这种代谢产物的总OTA排泄物的浓度范围与母体化合物相当。这是人类OTA 2相代谢产物的首次直接分析。