The metabolism of chlorpromazine N-oxide in man and dog.
The metabolism of chlorpromazine N-oxide in man and dog.
复制标题
N-氧化氯丙嗪在人和狗体内的代谢。
DOI：
10.3109/00498259009046817
复制
发表时间：
1990
期刊：
影响因子：
--
通讯作者：
K. Midha
中科院分区：
文献类型：
--
作者：
T. Jaworski;E. Hawes;G. Mckay;K. Midha
1.在雌性犬和成年男性中研究了单次经口给药后氯丙嗪N-氧化物的代谢。2.两个种属中存在广泛的代谢，在尿液和粪便中分别鉴别出4 - 7种代谢物。除氯丙嗪N-氧化物外，氯丙嗪N，S-二氧化物是唯一保留N-氧化物基团的分离代谢物。其他已鉴别代谢物为氯丙嗪及其7-羟基、亚砜、N-去甲基、7-羟基-N-去甲基和N-去甲基亚砜衍生物。3.对于犬样品，通过h.p.l.c.分离代谢物。并在质谱分析之前单独收集。对于人体样本，直接对代谢物进行h.p.l.c.-质谱测定所有代谢产物的结构均通过与真实样品的质谱和色谱行为直接比较来确认。4.在尿液和粪便中鉴别出的代谢物在两个种属中大部分相同，但仅在犬粪便中鉴别出氯丙嗪N-氧化物，仅在人尿液中鉴别出7-羟基-N-去甲基氯丙嗪。5.在人和狗的排泄物中观察到的N-氧化物化合物与先前研究的大鼠的观察结果形成对比，在大鼠中未检测到此类化合物。
1. The metabolism of chlorpromazine N-oxide was studied in female dogs and adult male humans after a single oral dose. 2. There was extensive metabolism in both species in that between four and seven metabolites were separately identified in urine and faeces. Apart from chlorpromazine N-oxide, chlorpromazine N,S-dioxide was the only isolated metabolite which retained the N-oxide group. The other identified metabolites were chlorpromazine and its 7-hydroxy, sulphoxide, N-desmethyl, 7-hydroxy-N-desmethyl and N-desmethylsulphoxide derivatives. 3. With dog samples, metabolites were separated by h.p.l.c. and individually collected prior to mass spectrometric analysis. With human samples, metabolites were directly subjected to h.p.l.c.-mass spectrometric determination. With all metabolites their structures were confirmed by direct comparison of their mass spectra and chromatographic behaviours with those of authentic samples. 4. The metabolites identified in urine and faeces were for the most part the same in both species, with the exceptions that chlorpromazine N-oxide was identified in the faeces of dog only and 7-hydroxy-N-desmethylchlorpromazine was identified in the urine of man only. 5. The observation of N-oxide compounds in the excreta of both man and dog contrasted with that for the previously studied rat, where no such compounds were detected.