BLOOD-BRAIN-BARRIER PENETRATION OF 3-AMINOPROPYL-N-BUTYLPHOSPHINIC ACID (CGP-36742) IN RAT-BRAIN BY MICRODIALYSIS MASS-SPECTROMETRY

The detection and quantitation of the novel drug 3-aminopropyl-n-butyl phosphinic acid (APBP), also known as CGP 36742, was performed in vivo using microdialysis and tandem mass spectrometry. This drug is a GABA -B antagonist with high specificity for GABA-B receptors. Animals rece ived doses of 100, 200, 500 and 1000 mg kg(-1) of the drug either intr avenously or per os (p.o.). Microdialysis probes, placed by stereotaxi s in either the frontal cortex or third ventricle of the rat, were use d to collect dialyzate samples over several hours. Samples were then a nalyzed by micro-electrospray tandem mass spectrometry to achieve a mo lecular mass and structure specific analysis. For example, animals rec eiving a dose of 100 mg kg(-1) p.o. showed a peak concentration of app roximately 10 mu M in the dialyzate. For comparison, tissue and plasma samples of the drug were measured under the same conditions using gas chromatography/mass spectrometry. This work demonstrates that the mic rodialysis technique in combination with the molecular specificity and high sensitivity of micro-electrospray tandem mass spectrometry can b e used to study the time course of the appearance of unmodified drug i n the brain of a single animal. (C) 1998 John Wiley & Sons, Ltd.