In broad terms, the MIST debate has typically focused on three areas: technologies (how to generate the necessary information to underwrite the safety of metabolites), timing (when to generate the necessary information) and strategy (what information is really needed and why). Although all three areas of debate are worthy of consideration, the purpose of this article is a more detailed focus on the application of new or existing technologies to address MIST issues, specifically one technology: accelerator MS (AMS). Initially used for radiocarbon dating [8], AMS was first applied to biomedical studies in the 1980s [9] before attracting the interest of drug metabolism and pharmacokinetics (DMPK) scientists in the late 1990s [10]. The application of the technology for generating absorption, distribution, metabolism and excretion (ADME) data via the quantitation of very low levels of isotopically labeled material (typically 14C) has been recognized for some time, as evidenced by literature examples (albeit somewhat surprisingly limited in number), where AMS has been applied to excretion balance studies and metabolite profiling [11–13]. As the MIST debate has intensified in recent years, AMS has inevitably been put forward as a potential solution to the issue of metabolite safety assessments during drug development.