Accelerator mass spectrometry (AMS) is an ultra-sensitive technique for quantitative analysis of low abundance isotopes that has found utility in very-low-level tracer (commonly referred to as microtracer) analysis in biological samples using, almost exclusively, 14C (the radioactive isotope of carbon; natural isotopic abundance ~10−12%). AMS was developed in the second half of the twentieth century and has been widely applied for radiocarbon dating in fields such as archaeology, wherein the 14C-content in organic matter within ancient artifacts is measured to determine their age [1]. Since the 1990s, AMS as a radiotracer technique has been applied in biomedical research to measure ultra-low concentrations of 14C in a wide range of biological samples. AMS sensitivity is unmatched because the technique measures the mass to charge ratio of atoms and typically an absolute count of approximately 1000 14C atoms in a sample provides an adequate signal-to-noise ratio for a valid measurement. An overview of biomedical AMS methodology is provided in the next section. This atom level measurement yields a method capable 700of quantifying 14C concentrations in the range of 10−16 to 10−18 g/mL. At a practical level this equates to lower limits of quantification (LLOQs) for total 14C measurements in biological samples (direct AMS; see Figure 27.1) 300–1000-fold lower than those typically obtained using liquid scintillation counting [2,3]. Despite impressive and on-going improvements in “conventional” liquid chromatography-tandem mass spectrometry (LC-MS/MS), the sensitivity of LC+AMS remains orders of magnitude lower, with LLOQs routinely in the sub-pg/mL range for the quantification of a specific small molecule analyte using LC+AMS [4].