Takechi K, Tamura H, Yamaoka K, Sakurai H
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Japan.
Free Radic Res. 1997 Jun;26(6):483-96. doi: 10.3109/10715769709097819.
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.
在药代动力学研究中，已使用了多种分析方法，包括放射性同位素检测和高效液相色谱法（HPLC）。在本研究中，我们开发了体内血液循环监测（BCM）-电子自旋共振（ESR）方法，这是一种利用传统X波段ESR光谱仪的新技术，用于在麻醉状态下观察活体大鼠循环血液中的稳定自由基。使用了带有各种取代基官能团的5-（PROXYL衍生物）和6-（TEMPO d衍生物）环状氮氧化物自旋探针。在获得自旋探针的物理化学性质，如超精细偶合常数（A值）、g值和分配系数，以及化合物在新鲜血液中的化学稳定性后，在正常大鼠中进行了体内BCM-ESR方法。获得了几个药代动力学参数，如探针的半衰期、分布容积、全身清除率和平均驻留时间，并根据其化学结构进行了讨论。此外，自旋探针的清除率与尿液浓度有关。发现BCM-ESR方法对于实时观察自由基非常有用。通过自旋探针随时间的ESR信号衰减，获得了药代动力学参数。
