Pharmacokinetic analysis of free radicals by in vivo BCM (Blood Circulation Monitoring)-ESR method.
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.
Takechi
K
K
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Japan.
Tamura
H
H
Yamaoka
K
K
Sakurai
H
H
D000818:Animals; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005292:Ferricyanides / Q000737:chemistry; D005609:Free Radicals / Q000097:blood* / Q000737:chemistry / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013113:Spin Labels
D005292:Ferricyanides; D005609:Free Radicals; D013113:Spin Labels; C007931:hexacyanoferrate III; D012710:Serum Albumin, Bovine