Metabolite ID

Met-ID is the process of detecting, structurally characterising and quantifying the metabolites formed when a compound is processed by biological systems such as liver microsomes, hepatocytes, plasma or in vivo models. 

Understanding the metabolite profile helps:

• assess whether metabolites could contribute to efficacy or toxicity 
• identify major human metabolites that may need further qualification
• compare species to support toxicology interpretation
• guide medicinal chemistry optimisation by identifying metabolic soft spots.

Met-ID is particularly important when new or disproportionate human metabolites are observed, or when regulators require a clear understanding of metabolite exposure.

An in vitro cross-species metabolism study compares the metabolites produced from the same drug candidate across human and animal test systems, typically hepatocytes or microsomes. It shows whether the animal species selected for toxicology produce the same metabolites as humans and at comparable levels. 

This information helps determine whether the non-clinical safety package is relevant to human exposure and whether additional studies may be needed to qualify human-specific or disproportionate metabolites before first-in-human studies. 

In vivo metabolite profiling characterises and quantifies the metabolites formed after dosing in a living organism. It is used to understand which metabolites circulate systemically, which tissues they reach and whether their exposure changes with dose or time. 

It is particularly relevant in later development, where regulators may expect a better understanding of human metabolite exposure and whether any circulating metabolites could raise safety concerns. 

MIST refers to the FDA and ICH concept that human metabolites present at disproportionately higher levels than in the toxicology species may need additional safety assessment. 

Under current expectations, metabolites that represent more than 10% of total drug-related exposure in humans may need to be evaluated if they are not adequately covered in the non-clinical species used in safety studies. Meeting MIST expectations generally requires integrated metabolite profiling across in vitro, preclinical and clinical studies.