High-performance liquid chromatography study of the pharmacokinetics of various spin traps for application to in vivo spin trapping.
In vivo spin trapping is potentially a very useful tool to investigate the role of free radicals in physiologic processes and disease development. Unfortunately, knowledge on the stability and distribution of spin traps in living systems is limited. Therefore, in our study, we selected 11 acyclic and cyclic nitrone spin traps with diverse properties to determine their pharmacokinetics in mice. At varying times after intraperitoneal administration, we measured the concentration of the spin traps in the liver, heart, and blood. Our results showed that most spin traps were rapidly absorbed and were approximately evenly distributed throughout the mouse body. It was also found that most of the traps were relatively stable in vivo with more than half of the injected amount still available for spin trapping free radicals after an hour. Two of the 11 tested spin traps, however, decomposed after injection. These results indicate that for a successful in vivo spin trapping experiment, the stability of the spin trap is not of major concern, but the time course of distribution may be important.
Liu
K J
KJ
Department of Radiology, Dartmouth College, Hanover, NH 03755, USA. jim.liu@dartmouth.edu
Kotake
Y
Y
Lee
M
M
Miyake
M
M
Sugden
K
K
Yu
Z
Z
Swartz
H M
HM
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003497:Cyclic N-Oxides / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009589:Nitrogen Oxides / Q000493:pharmacokinetics*; D011725:Pyridines; D013113:Spin Labels
D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D011725:Pyridines; D013113:Spin Labels; C043438:alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone; C029217:phenyl-N-tert-butylnitrone; C017245:5,5-dimethyl-1-pyrroline-1-oxide