Pharmacokinetic analysis of free radicals by in vivo BCM (Blood Circulation Monitoring)-ESR method

Free Radic Res. 1997 Jun;26(6):483-96. doi: 10.3109/10715769709097819.

Abstract

In pharmacokinetic studies, a variety of analytical method including radioisotopic detection and HPLC (high performance liquid chromatography) has been used. In the present investigation, we developed in vivo BCM (Blood Circulation Monitoring)-ESR method, which is a new technique with a conventional X-band ESR spectrometer for observing stable free radicals in the circulating blood of living rats under anaesthesia. Both 5-(PROXYL derivatives) and 6-(TEMPO d derivatives) membered nitroxide spin probes with various types of substituent functional group were used. After physico-chemical properties of the spin probes such as hyperfine coupling constant (A-value), g-value and partition coefficient as well as chemical stability of the compounds in the fresh blood were obtained, the in vivo BCM-ESR method was performed in normal rats. Several pharmacokinetic parameters such as half-life of the probes, distribution volume, total body clearance and mean residence time were obtained and discussed in terms of their chemical structures. In addition, clearance of a spin probe was related to the urine concentration. The BCM-ESR method was found to be very useful to observe free radicals at the real time. By time-dependent ESR signal decay of spin probes, pharmacokinetic parameters were obtained.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electron Spin Resonance Spectroscopy / methods*
  • Ferricyanides / chemistry
  • Free Radicals / blood*
  • Free Radicals / chemistry
  • Free Radicals / urine
  • Rats
  • Rats, Wistar
  • Serum Albumin, Bovine / chemistry
  • Spin Labels

Substances

  • Ferricyanides
  • Free Radicals
  • Spin Labels
  • hexacyanoferrate III
  • Serum Albumin, Bovine