Analysis of (R)-4-oxo-5-phosphononorvaline (MDL 100,453) in rat plasma and brain dialysate using liquid chromatography after derivatization with 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 antagonist of N-methyl-D-aspartate receptor, in rat plasma and brain dialysate. The plasma samples were deproteinized with acetonitrile and then derivatized with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC). The brain dialysis samples were dried in vacuum, reconstituted with borate buffer, and derivatized with AQC. The derivatized MDL 100,453 was analyzed by LC with a Nova-Pak C18 column at 32 degrees C using a gradient mobile phase. Detection was accomplished by fluorescence with excitation at 250 nm and emission at 395 nm. This analytical method was used to follow the time course of drug concentrations in rat plasma and brain dialysate after intravenous (i.v.) bolus injection of MDL 100,453 or a combination of i.v. bolus injection and i.v. infusion.
Cornelius
K E
KE
Marion Merrell Dow Research Institute, Cincinnati, OH 45215-6300, USA.
Fadayel
G M
GM
Baron
B M
BM
Schmidt
C J
CJ
Haegele
K D
KD
Chen
T M
TM
D000634:Aminoquinolines; D000818:Animals; D001923:Brain Chemistry; D002219:Carbamates; D002851:Chromatography, High Pressure Liquid; D003956:Dialysis; D018691:Excitatory Amino Acid Antagonists / Q000032:analysis* / Q000097:blood; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D013050:Spectrometry, Fluorescence; D014633:Valine / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood
C078178:6-aminoquinolyl-N-hydroxysuccinimidyl carbamate; D000634:Aminoquinolines; D002219:Carbamates; D018691:Excitatory Amino Acid Antagonists; D007202:Indicators and Reagents; C066280:4-oxo-5-phosphononorvaline; D014633:Valine