Abstract：
Sodium (S)- 2-(dithiocarboxylato((2 S,3 R,4 R,5 R)- 2,3,4,5,6-pentahydroxyhexyl)amino)- 4(methylthio)butanoate (GMDTC) is a compound that removes cadmium from kidney cells. This study aims to investigate the metabolic stability and metabolite identification of GMDTC in various liver microsomes, including those from human, monkey, dog, rat and mouse. The results show that the T1/2 values of GMDTC in human, monkey, dog, rat and mouse liver microsomes were 16.54, 18.14, 16.58, 15.16 and 16.00 min, respectively. While the hepatic extraction ratios (ERh) of GMDTC measured after 60 min incubation in these liver microsomes were 0.82, 0.70, 0.80, 0.75 and 0.79, respectively, indicating that GMDTC exhibits rapid hepatic metabolism and high hepatic clearance with no significant interspecies differences. Subsequent metabolite identification by high-resolution mass spectrometry revealed the presence of three metabolites, designated M1∼M3. The major metabolite products of GMDTC were found to be M1 and M2. The relative abundances of the hydrolysis products (M1 and M2) in human, monkey, dog, rat and mouse liver microsomes were found to be 97.18%, 97.99%, 95.94%, 96.31% and 93.43%, respectively, indicating that hydrolysis is the primary metabolic pathway of GMDTC in liver microsomes in vitro, and with no significant interspecies differences.
摘要：
钠（S）-2-（二硫代羧基（（2S，3R,4R,5R）-2,3,4,5,6-五羟基己基）氨基）-4（甲硫基丁酸酯（GMDTC）是一种从肾细胞中去除镉的化合物。本研究旨在探讨GMDTC在各种肝微粒体中的代谢稳定性和代谢产物鉴定。包括那些来自人类的，猴子,狗,老鼠和老鼠结果表明,人类GMDTC的T1/2值,猴子,狗,大鼠和小鼠肝微粒体分别为16.54、18.14、16.58、15.16和16.00分钟，分别。而在这些肝微粒体中孵育60分钟后测量的GMDTC的肝提取率（ERh）分别为0.82、0.70、0.80、0.75和0.79，表明GMDTC表现出快速的肝代谢和高的肝清除率，没有明显的种间差异。随后通过高分辨率质谱对代谢物进行鉴定，发现存在三种代谢物，指定为M1~M3。发现GMDTC的主要代谢产物是M1和M2。人类水解产物(M1和M2)的相对丰度，猴子,狗,发现大鼠和小鼠肝微粒体为97.18%，97.99%,95.94%,96.31%和93.43%，分别,表明水解是肝微粒体中GMDTC的主要代谢途径，并且没有明显的种间差异。
