IN-VIVO MICRODIALYSIS AND LIQUID-CHROMATOGRAPHY THERMOSPRAY MASS-SPECTROMETRY OF THE NOVEL ANTICONVULSANT 2,3 ,5-BIS-O-(1-METHYLETHYLIDENE)-BETA-D-FRUCTOPYRANOS SULFAMATE (TOPIRAMATE) IN RAT-BRAIN FLUID/

The concentration of a novel anticonvulsant, 2,3: 5-bis-O-(1-methyleth ylidene)-beta-D-fructopyranose sulfamate (topiramate), was determined in the extracellular fluid of rat brain by in vivo microdialysis combi ned off-line with liquid chromatography/thermospray mass spectrometry. A microdialysis probe was stereotaxically implanted in the nucleus ac cumbens region of the rat brain. The maximum concentration of topirama te in the brain dialysate for a dose of 50 mg kg(-1) i.v. was similar to 10 mu M and occurred 45 min post-injection. The detection limit of topiramate in the extracellular fluid of rat brain was in the 0.1 mu M range using selected ion monitoring techniques. The base peak, which was the ammonium adduct ion [M + NH4](+), was used for detection. An i nternal standard of d(12)-labeled topiramate was utilized for quantita tion by isotope dilution analysis. (C) 1998 John Wiley & Sons, Ltd.