The use of capillary high performance liquid chromatography with electrospray mass spectrometry for the analysis of small volume blood samples from serially bled mice to determine the pharmacokinetics of early discovery compounds.

The methodology described demonstrates, for the first time, the feasibility of performing pharmacokinetic studies in the serially bled mouse model to support the early development of discovery compounds. Sample analysis, using capillary high performance liquid chromatography combined with tandem mass spectrometry, has facilitated the achievement of this milestone and has successfully been applied to determine pharmacokinetic information following both intravenous and oral administration of a single discovery compound. The methodologies described demonstrate potential for a reduction in the amount of new chemical entity required to undertake pharmacokinetic studies.