Curcumin (Cur) is a natural anticancer pigment, but its poor absorption and extensive metabolism limit its clinical applications. In this study, an ultra‐high performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry method was employed to investigate the metabolic profiles of a Cur self‐emulsifying drug delivery system (C‐SEDDS) in rat plasma, urine, bile and feces after oral administration at 100 mg/kg. Protein precipitation, solid‐phase and ultrasonic extractions were used to prepare different biosamples. A total of 34 metabolites were identified using available reference standards, or tentatively identified based on the mass spectrometric fragmentation patterns and the chromatographic elution order. Nine metabolites of Cur were found for the first time in vivo. Glucuronidation, sulfation, reduction, dehydroxylation, demethylation, demethoxylation and methylation were its possible metabolic reactions. Moreover, the differences were compared in terms of plasma metabolites found in C‐SEDDS‐treated, Cur suspension‐treated and rats treated with a commercial curcuminoid phospholipid complex administered at the same oral dose. Dihydrocurcumin (DHC), DHC glucuronide and methylated DHC were found only in the metabolic profile of C‐SEDDS‐treated rat plasma, suggesting that different drug delivery systems may cause a change in Cur metabolic pathways. This study provides a sensitive and rapid method for the identification of Cur metabolites in biosamples.

中文翻译：

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超高效液相色谱/四极杆飞行时间质谱测定姜黄素自乳化药物递送系统的代谢谱

姜黄素（Curcumin，Cur）是一种天然的抗癌色素，但其吸收不良和广泛的新陈代谢限制了其临床应用。在这项研究中，采用超高效液相色谱/四极杆飞行时间质谱法研究了大鼠血浆，尿液，胆汁和尿液中的Cur自乳化药物递送系统（C-SEDDS）的代谢谱。口服后100毫克/千克的粪便。蛋白质沉淀，固相萃取和超声萃取用于制备不同的生物样品。使用可用的参考标准物鉴定了总共34种代谢物，或根据质谱碎裂模式和色谱洗脱顺序初步鉴定了这些代谢物。首次在体内发现9种Cur的代谢产物。葡萄糖醛酸化，硫酸化，还原，脱羟基，脱甲基，脱甲氧基和甲基化是其可能的代谢反应。此外，比较了在以相同口服剂量经C-SEDDS治疗，Cur悬浮液治疗和以市售姜黄素磷脂复合物治疗的大鼠中发现的血浆代谢物方面的差异。仅在经C-SEDDS处理的大鼠血浆的代谢谱中发现了二氢姜黄素（DHC），DHC葡糖醛酸苷和甲基化DHC，这表明不同的药物递送系统可能会导致Cur代谢途径的改变。这项研究提供了一种灵敏而快速的鉴定生物样品中Cur代谢物的方法。