Mattocks A R, Jukes R
Toxicology Unit, MRC Laboratories, Carshalton, Surrey, U.K.
Chem Biol Interact. 1990;75(2):225-39. doi: 10.1016/0009-2797(90)90120-c.
Reactive pyrrolic metabolites formed when pyrrolizidine alkaloids are given to rats can alkylate soluble and tissue-bound thiol groups. Pyrrolic thioethers thus formed are relatively stable, and may persist in tissues for long periods. A simple procedure has been developed for recovering the nucleus of the pyrrolic metabolite from such S-binding, whether in solution or attached to solid tissues, in an easily identifiable form. The thioether bond was broken by silver nitrate and the pyrrolic moiety allowed to react with ethanol or methanol to form an ethoxy or methoxy derivative. The chemical basis of the procedure was established by model experiments on a preparative scale, but for small scale recovery from tissues, pyrrolic ethers were extracted and identified by TLC, HPLC, capillary GC and mass spectrometry. Because the pyrrolic derivatives thus formed were easily recognised and unrelated to any physiological compound, the recovery method described, especially when applied to blood samples, provided a way to monitor animals for previous exposure to toxic pyrrolizidine alkaloids.
给大鼠投喂吡咯里西啶生物碱时形成的反应性吡咯代谢产物可使可溶性和组织结合的硫醇基团烷基化。由此形成的吡咯硫醚相对稳定，可能会在组织中长期存在。已开发出一种简单的方法，用于从这种硫结合物中以易于识别的形式回收吡咯代谢产物的核心，无论其是在溶液中还是附着于固体组织上。硫醚键被硝酸银打断，吡咯部分与乙醇或甲醇反应形成乙氧基或甲氧基衍生物。该方法的化学基础通过制备规模的模型实验得以确立，但对于从组织中进行小规模回收，吡咯醚通过薄层色谱法（TLC）、高效液相色谱法（HPLC）、毛细管气相色谱法和质谱法进行提取和鉴定。由于如此形成的吡咯衍生物易于识别且与任何生理化合物无关，所描述的回收方法，尤其是应用于血样时，提供了一种监测动物既往是否接触有毒吡咯里西啶生物碱的方法。
