Application of liquid chromatography-accelerator mass spectrometry (LC-AMS) to evaluate the metabolic profiles of a drug candidate in human urine and plasma.
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.
Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Groton, CT 06340, USA. chandra.prakash@pfizer.com
Chandra
C
Prakash
Christopher L
CL
Shaffer
Larry M
LM
Tremaine
Rosa G
RG
Liberman
Paul L
PL
Skipper
Jimmy
J
Flarakos
Steven R
SR
Tannenbaum
D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000191:economics / Q000379:methods*; D010315:Particle Accelerators; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000378:metabolism; D013997:Time Factors
D002250:Carbon Radioisotopes; D004364:Pharmaceutical Preparations