Metformin, a first-line drug used to treat type 2 diabetes, is not metabolised in the body and discharged into the environment in the form of prototype drugs. Compounds C (C4H6ClN3) and Y (C4H6ClN5) are the main disinfection byproducts of metformin in urban sewage treatment; however, their potential toxicity is unclear. In this study, absorption, distribution, metabolism, elimination, and toxicity (ADMET) prediction indicated that compounds C and Y had potential hepatotoxicity and could cross the blood-brain-barrier. Toxicity verification tests indicated a sex difference in the acute toxicity of compound C, with an LD50 value of 253.269 mg kg-1 for male mice and 728.908 mg kg-1 for female mice. The subacute toxicity of compounds C and Y was evaluated to study the toxicity mechanism via the gut-liver-brain axis, which indicated that they could cause damage to the liver and brain, change the composition of the gut microbiota, and disturb the levels of metabolites in mice. Neuron-like magnetic N-doped biochar (NiFe-LDOs/N-BC) was synthesised using hydrothermal and calcination methods, and the optimised d-MSPE-HPLC-UV method was proven to be applicable for the trace detection of compound C in real water samples. The simultaneous presentation of toxicity evaluation and trace detection of compound C is intended to make the monitoring system for compound C more comprehensive.

中文翻译：

---

二甲双胍环境中消毒副产物：肠-肝-脑轴稳态的系统毒性评价及基于NiFe-LDOs/N-BC复合材料的检测方法的建立


二甲双胍是用于治疗 2 型糖尿病的一线药物，不会在体内代谢，而是以原型药物的形式排放到环境中。化合物C（C4H6ClN3）和Y（C4H6ClN5）是城市污水处理中二甲双胍的主要消毒副产物;然而，它们的潜在毒性尚不清楚。在这项研究中，吸收、分布、代谢、消除和毒性 （ADMET） 预测表明化合物 C 和 Y 具有潜在的肝毒性，可以穿过血脑屏障。毒性验证试验表明化合物 C 的急性毒性存在性别差异，雄性小鼠的 LD50 值为 253.269 mg kg-1，雌性小鼠的 LD50 值为 728.908 mg kg-1。评价化合物 C 和 Y 的亚急性毒性，研究通过肠-肝-脑轴的毒性机制，表明它们可能对肝脏和大脑造成损害，改变肠道菌群的组成，并扰乱小鼠的代谢物水平。采用水热法和煅烧法合成了神经元样磁性 N 掺杂生物炭 （NiFe-LDOs/N-BC），优化的 d-MSPE-HPLC-UV 方法被证明适用于实际水样中化合物 C 的痕量检测。化合物 C 的毒性评价和痕量检测同时呈现，旨在使化合物 C 的监测系统更加全面。