Kroll C, Borchert H H
Department of Pharmacy of the Humboldt University of Berlin, Goethestr. 54, 13086 Berlin, Germany. christina=
Eur J Pharm Sci. 1999 Apr;8(1):5-9. doi: 10.1016/s0928-0987(98)00047-5.
The formation of new metabolites of the stable nitroxyl radical 4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPONE) inside the isolated perfused rat liver was examined. The paramagnetic 4-hydroxy derivative (TEMPOL) and the diamagnetic 1,4-dihydroxy derivative were found to be the major metabolites besides the well-known corresponding hydroxylamine of TEMPONE. No reoxidation of the hydroxyl group in the 4-position was observed. The conversion of nitroxides to the sterically hindered secondary amines remains speculative. A redox cycle of nitroxide and hydroxylamine including the secondary amines is discussed. For the first time the biotransformation of the stable nitroxyl radical TEMPONE detected by means of GC and GC-MS has been examined and new metabolites have been described, i.e. the newly discussed metabolites have to be considered for the interpretation of electron paramagnetic resonance (EPR), magnetic resonance imaging (MRI) and dynamic nuclear polarization (DNP) measurements on using the spin probe TEMPONE.
研究了在离体灌注大鼠肝脏内稳定的硝酰自由基4-氧代-2,2,6,6-四甲基哌啶-N-氧自由基（TEMPONE）新代谢产物的形成。除了众所周知的TEMPONE相应羟胺外，顺磁性的4-羟基衍生物（TEMPOL）和抗磁性的1,4-二羟基衍生物被发现是主要代谢产物。未观察到4位羟基的再氧化。硝酰自由基向位阻仲胺的转化仍具有推测性。讨论了包括仲胺在内的硝酰自由基和羟胺的氧化还原循环。首次通过气相色谱（GC）和气相色谱-质谱联用（GC-MS）检测了稳定硝酰自由基TEMPONE的生物转化，并描述了新的代谢产物，即在使用自旋探针TEMPONE进行电子顺磁共振（EPR）、磁共振成像（MRI）和动态核极化（DNP）测量的解释中，必须考虑新讨论的代谢产物。
