HPLC PROCEDURE FOR THE PHARMACOKINETIC STUDY OF THE SPIN-TRAPPING AGENT, ALPHA-PHENYL-N-TERT-BUTYL NITRONE (PBN)

被引:25
作者
CHEN, GM [1 ]
GRIFFIN, M [1 ]
POYER, JL [1 ]
MCCAY, PB [1 ]
机构
[1] OKLAHOMA MED RES FDN,MOLEC TOXICOL LAB,OKLAHOMA CITY,OK 73104
关键词
HPLC analysis; PBN disposition; Pharmacokinetics; Spin-trapping agent; Time course; Tissue concentration;
D O I
10.1016/0891-5849(90)90110-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Considerable progress has been made in the use of spin-trapping agents for the trapping of free radicals in biological systems. Radicals have been detected in both in vitro and in vivo systems using this methodology. Free radicals have not only been identified by this procedure, but also theintensity of radical generation and the duration of their production has been assessed as well. One of the most widely used spin-trapping agents in biogical systems is PBN. This spin trap appears to be relatively nontoxic at the levels required for successful trapping experiments, but there is no information concerning the possible fate of PBN in such biological systems. Metabolism of PBN could alter the concentration of PBN at the site of trapping which may affect the efficiency of radical capture, especially in in vivo systems. In this study, PBN was administered intraperitoneally to rats and the concentration of the spin trap in various organs was determined by high pressure liquid chromatography as a function fo time (15 min to 12 h). The concentration of PBN in plasma peaked at 15 min while the maximum in all organs tested occurred at 30 min. The time course of PBN concentrations in all tissues followed similar curves, and declined rather steeply after the 30-min maximum with a biological half-life of 134 min. However, the amount of PBN per gram of tissue was always higher in liver and kidney than in the brain, heart, and lung. PBN was detected in the urine for as long as 24 h after injection of the compound. © 1990.
引用
收藏
页码:93 / 98
页数:6
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