Bioanalytical applications of accelerator mass spectrometry for pharmaceutical research

Accelerator mass spectrometry (AMS) is a mass spectrometric method for quan tifying isotopes. It has had great impact in the geosciences and is now bei ng applied in the biomedical fields. AMS measures radioisotopes such as C-1 4, H-3, C-41, and Cl-36, and others, with attomole sensitivity and high pre cision. Its use is allowing absorption, distribution, metabolism and elimin ation studies, as well as detailed pharmacokinetics, to be carried out dire ctly in humans with very low chemical or radiological hazard. It is used in combination with standard separation methodologies, such as chromatography , in identification of metabolites and molecular targets for both toxicants and pharmacologic agents. AMS allows the use of very low specific activity chemicals (less than or equal to 1 mCi/mmol), creating opportunities to us e compounds not available in a high specific activity form, such as those t hat must be biosynthesized, produced in combinatorial libraries, or made th rough inefficient synthesis. AMS is allowing studies to be carried out with agents having low bioavailability, low systemic distributions, or high tox icity where administered doses must be kept low (less than or equal to 1 mu g/kg). It may have uses in tests for idiosyncratic metabolism, drug intera ction, or individual susceptibility, among others. The ability to use very low chemical doses, low radiological doses, small samples and conduct multi ple dose studies may help move drug candidates into humans faster and safer than before. The uses of AMS are growing and its potential for drug develo pment is only now beginning to be realized.