Comparison of the effects of perfusion in determining brain penetration (brain-to-plasma ratios) of small molecules in rats.

In the process of drug discovery, brain and plasma measurements of new chemical entities in rodents are of interest, particularly when the target receptors are in the brain. Brain-to-plasma ratios (B/P) obtained from a rodent pharmacokinetic assay are useful in helping determine which compounds are brain penetrant. The study reported here was performed to determine whether whole-body saline perfusion for complete blood removal was required to accurately measure brain tissue compound concentrations.

Rapid pharmacokinetic screening for the selection of new drug discovery candidates using a generic isocratic liquid chromatography--atmospheric pressure ionization tandem mass spectrometry method.

A generic isocratic HPLC-APCI-MS-MS method has been developed for the determination of plasma concentrations of bioactive compounds for the selection of potential new drug discovery candidates. A 4.6 x 50 mm cyano phase column eluted with an acetonitrile/water mobile phase containing 20 mM ammonium acetate and 0.