使用6-氨基喹啉-N-羟基琥珀酰亚胺基氨基甲酸酯衍生化后，通过液相色谱法分析大鼠血浆和脑透析液中的（R）-4-氧代-5-膦酰基正缬氨酸（MDL 100,453）。

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.

作者信息

Cornelius K E, Fadayel G M, Baron B M, Schmidt C J, Haegele K D, Chen T M

机构信息

Marion Merrell Dow Research Institute, Cincinnati, OH 45215-6300, USA.

出版信息

J Pharm Biomed Anal. 1995 Dec;14(1-2):143-50. doi: 10.1016/0731-7085(95)01604-X.

DOI:10.1016/0731-7085(95)01604-X

PMID:8833976

Abstract

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.

摘要

已开发出一种采用柱前衍生化和荧光检测的液相色谱（LC）方法，用于定量测定大鼠血浆和脑透析液中的（R）-4-氧代-5-膦酰基正缬氨酸（MDL 100,453），它是N-甲基-D-天冬氨酸受体的选择性拮抗剂。血浆样品用乙腈脱蛋白，然后用6-氨基喹啉-N-羟基琥珀酰亚胺基氨基甲酸酯（AQC）进行衍生化。脑透析样品在真空中干燥，用硼酸盐缓冲液复溶，并用AQC进行衍生化。衍生化后的MDL 100,453采用Nova-Pak C18柱在32℃下通过梯度流动相进行LC分析。通过在250nm激发和395nm发射的荧光进行检测。该分析方法用于跟踪静脉推注MDL 100,453或静脉推注与静脉输注联合给药后大鼠血浆和脑透析液中药物浓度的时间进程。