Zhang Keyu, Li Sumei, Zheng Wenli, Zhang Lifang, Wang Chunmei, Wang Xiaoyang, Fei Chenzhong, Xue Feiqun, Wang Mi
Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
Rapid Commun Mass Spectrom. 2014 Aug 15;28(15):1723-34. doi: 10.1002/rcm.6953.
Nitromezuril is a novel triazine compound possessing remarkable anticoccidial activity that could have possible future use in the prevention of coccidiosis; however, its metabolic characteristics have still not been revealed.
In the present study, the in vitro metabolism of nitromezuril in HepG2 cells, rat S9 and primary hepatocytes was investigated using high-performance liquid chromatography with electrospray ionization tandem mass spectrometry. The structures of metabolites and their product ions were easily and reliably characterized based on the accurate MS(2) spectra and known structure of nitromezuril.
As expected, three metabolites (M1-M3) were detected in a HepG2 cells system, one metabolite was respectively detected and identified as M1 in rat S9 and M2 in rat primary hepatocytes. M1 and M2 were confirmed respectively based on comparing their retention times, full scan, product ion scan with available authentic standards and M3 was tentatively identified as hydroxyl compound of M2.
Pathways of nitromezuril were reported for the first time and no obvious species difference was shown. The proposed metabolic pathways of nitromezuril can be expected to play a key role in pharmacodynamics and food safety evaluations.
硝美珠利是一种新型三嗪化合物，具有显著的抗球虫活性，未来可能用于预防球虫病；然而，其代谢特征尚未揭示。
在本研究中，采用高效液相色谱-电喷雾电离串联质谱法研究了硝美珠利在HepG2细胞、大鼠S9和原代肝细胞中的体外代谢。基于精确的MS(2)谱和硝美珠利的已知结构，很容易且可靠地表征了代谢物及其产物离子的结构。
正如预期的那样，在HepG2细胞系统中检测到三种代谢物（M1-M3），在大鼠S9中分别检测到一种代谢物并鉴定为M1，在大鼠原代肝细胞中鉴定为M2。通过比较它们的保留时间、全扫描、产物离子扫描与可用的标准品，分别确认了M1和M2，M3初步鉴定为M2的羟基化合物。
首次报道了硝美珠利的代谢途径，未显示明显的种属差异。所提出的硝美珠利代谢途径有望在药效学和食品安全评估中发挥关键作用。
