Biomedical accelerator mass spectrometry: recent applications in metabolism and pharmacokinetics

Expert Opin Drug Metab Toxicol. 2008 Aug;4(8):1021-33. doi: 10.1517/17425255.4.8.1021.


Background: Accelerator mass spectrometry (AMS) is a sensitive isotope ratio technique used in drug development that allows for small levels of 14C-drug to be administered to humans, thereby removing regulatory hurdles associated with radiotracer studies. AMS uses innovative study designs to obtain pharmacokinetic and metabolism data.

Objective: This review addresses the metabolism and pharmacokinetics relevant to cases where therapeutic drug concentrations are achieved in humans.

Methods: The review focuses on two study designs: i) administration of tracer 14C-drug intravenously with a simultaneous non-labelled extravascular therapeutic dose to obtain the pharmacokinetic parameters of clearance, volume of distribution and absolute bioavailability without extensive intravenous toxicology safety studies or formulation development; and ii) use of low levels of 14C-drug during Phase I studies to investigate the quantitative metabolism of the drug in humans early in drug development, as required by the new FDA guideline issued in February 2008.

Results/conclusions: Early knowledge about a drug's clearance, volume of distribution, absolute bioavailability and metabolism can affect the development of a new drug candidate.

Publication types

  • Review

MeSH terms

  • Biological Availability
  • Carbon Radioisotopes / metabolism
  • Clinical Trials, Phase I as Topic
  • Drug Design*
  • Guidelines as Topic
  • Humans
  • Injections, Intravenous
  • Mass Spectrometry / methods*
  • Pharmacokinetics*
  • Tissue Distribution
  • United States
  • United States Food and Drug Administration


  • Carbon Radioisotopes