Instruments for radiation measurement in life sciences (4). VI. Use of Accelerator mass spectrometry in studies on drug metabolism and pharmacokinetics

Non-clinical and clinical uses of accelerator mass spectrometry (AMS) are described mainly on studies of drug metabolism and pharmacokinetics from a view of new drug development. AMS is applicable as a highly sensitive method to measure plasma drug concentrations. Measurement of 14C-labeled compounds less than 1 dpm/sample or of parathyroid hormone-related protein (PTHrP), in combination of AMS and radioimmunoassay without radioactive waste release is described as an example. Cases of measuring DNA-adduct are also described involving human studies using 14C-mutagen (a quinoxaline derivative derived from burned amino acid, given in a microdose of 304 ng/kg, 4.3 μCi/body). Plasma concentration measurement, mass balance study and metabolite identification of 14C-GI1817771 (a drug candidate) are a typical AMS application for a pharmacokinetic study in human in a microdose (121 Bq/body). Metabolites of 14C-compound A in rat platelet are identified by the author. As above, AMS makes it possible to conduct the pharmacokinetic study in human at a microdose with no significant radiation exposure, which will promote the efficient new drug development. (N.I.)