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Application of Liquid Chromatography-Accelerator Mass Spectrometry (LC-AMS) to Evaluate the Metabolic Profiles of a Drug Candidate in Human Urine and Plasma

2007; Bentham Science Publishers; Volume: 1; Issue: 3 Linguagem: Inglês

10.2174/187231207781369735

1874-0758

Christopher L. Shaffer, Larry M. Tremaine, Rosa G. Liberman, Paul L. Skipper, Jimmy Flarakos, Steven R. Tannenbaum,

Metabolism and Genetic Disorders

Metabolite profiling of 100- and 1,000-fold diluted urine and plasma samples from a conventional radiolabeled human ADME study is described using a highly sensitive LC-AMS technique. The concentration of radioactivity and the metabolic profiles in urine and plasma determined using this technique were similar to those employing standard off-line (i.e. LSC) or in-line (i.e. beta-RAM or LC-ARC dynamic-flow) radioactivity monitoring techniques. The results indicate that at a simulated ca. 100 nCi clinical dose, plasma and urine concentrations of (14)C, as well as their metabolic profiles, may be determined routinely by LC-AMS. This approach opens the possibility of using LC-AMS for both the high-throughput quantitation of biological samples and the generation of high-resolution chromatographic profiles of complex mixtures at a lower cost than current AMS analyses that require the conversion of sample carbon to graphite, a laborious and time consuming process.