Disinfection by-products of metformin in the environment: A systematic toxicity evaluation on gut-liver-brain axis homeostasis and establishment of a detection method based on NiFe-LDOs/N-BC composite.

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.