ANALYSIS OF (R)-4-OXO-5-PHOSPHONONORVALINE (MDL-100,453) IN RAT PLASMA AND BRAIN DIALYSATE USING LIQUID-CHROMATOGRAPHY AFTER DERIVATIZATIONWITH 6-AMINOQUINOLYL-N-HYDROXYSUCCINIMIDYL CARBAMATE

A liquid chromatographic (LC) method with precolumn derivatization and fluorescence detection has been developed for the quantitation of (R) -4-oxo-5-phosphononorvaline (MDL 100,453), which is a selective antago nist of N-methyl-D-aspartate receptor, in rat plasma and brain dialysa te. The plasma samples were deproteinized with acetonitrile and then d erivatized with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC). The brain dialysis samples were dried in vacuum, reconstituted with b erate buffer, and derivatized with AQC. The derivatized MDL 100,453 wa s analyzed by LC with a Nova-Pak C-18 column at 32 degrees C using a g radient mobile phase. Detection was accomplished by fluorescence with excitation at 250 nm and emission at 395 nm. This analytical method wa s used to follow the time course of drug concentrations in rat plasma and brain dialysate after intravenous (i.v.) bolus injection of MDL 10 0,453 or a combination of i.v. bolus injection and i.v. infusion.