Lay J O, Korfmacher W A, Miller D W, Siitonen P, Holder C L, Gosnell A B
Biomed Environ Mass Spectrom. 1986 Nov;13(11):627-32. doi: 10.1002/bms.1200131108.
Three glucuronide metabolites of doxylamine succinate were collected in a single fraction using high-performance liquid chromatography (HPLC) from the urine of dosed male Fischer 344 rats. The metabolites were then separated using an additional HPLC step into fractions containing predominantly a single glucuronide metabolite. Analysis of the metabolites by methane and ammonia desorption chemical ionization, with and without derivatization, revealed fragment ions suggestive of a hydroxylated doxylamine moiety. Identification of the metabolites as glucuronides of doxylamine, desmethyldoxylamine and didesmethyldoxylamine was accomplished, based on determination of the molecular weight and exact mass of each metabolite using fast atom bombardment (FAB) ionization. This assignment was confirmed by the fragmentation observed in FAB mass spectrometric and tandem mass spectrometric experiments. Para-substitution of the glucuronide on the phenyl moiety was observed by 500-MHz nuclear magnetic resonance (NMR) spectrometry. A fraction containing all three glucuronide metabolites, after a single stage of HPLC separation, was also analysed by FAB mass spectrometry, and the proton- and potassium-containing quasimolecular ions for all three metabolites were observed.
使用高效液相色谱法（HPLC）从经给药的雄性Fischer 344大鼠尿液中收集到琥珀酸多西拉敏的三种葡萄糖醛酸代谢物，并将其集中在单一馏分中。然后通过另一HPLC步骤将这些代谢物分离成主要含有单一葡萄糖醛酸代谢物的馏分。通过甲烷和氨解吸化学电离对代谢物进行分析，无论有无衍生化，均显示出提示羟基化多西拉敏部分的碎片离子。基于使用快原子轰击（FAB）电离法测定每种代谢物的分子量和精确质量，确定这些代谢物为多西拉敏、去甲基多西拉敏和双去甲基多西拉敏的葡萄糖醛酸。FAB质谱和串联质谱实验中观察到的碎片对该归属进行了确认。通过500兆赫核磁共振（NMR）光谱法观察到葡萄糖醛酸在苯基部分上的对位取代。在HPLC分离的单一阶段后，对含有所有三种葡萄糖醛酸代谢物的馏分也进行了FAB质谱分析，并观察到所有三种代谢物的含质子和含钾准分子离子。
