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大鼠体内氯丙嗪氮氧化物的代谢

The metabolism of chlorpromazine N-oxide in the rat.

作者信息

Jaworski T J, Hawes E M, McKay G, Midha K K

机构信息

College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.

出版信息

Xenobiotica. 1988 Dec;18(12):1439-47. doi: 10.3109/00498258809042266.

DOI:10.3109/00498258809042266
PMID:3266695
Abstract
  1. The metabolism of chlorpromazine N-oxide was studied in female rats after a 20 mg/kg single oral dose. 2. Metabolites identified in both urine and faeces were chlorpromazine, 7-hydroxychlorpromazine, chlorpromazine sulphoxide, N-desmethylchlorpromazine and N-desmethylchlorpromazine sulphoxide. 3. Metabolites were separated by h.p.l.c. or g.l.c. prior to mass spectrometric analysis. The structures of the metabolites were confirmed by direct comparison of their mass spectra and chromatographic behaviours with those of authentic compounds. 4. Chlorpromazine N-oxide and any metabolite which retained the intact N-oxide function, such as chlorpromazine, N,S-dioxide, could not be identified in any of the extracts. 5. When 3H-chlorpromazine N-oxide was administered under the same conditions; approximately twice as much radioactivity was excreted in the faeces (52.1 +/- 9.7%) as in the urine (26.9 +/- 7.2%).
摘要
  1. 对雌性大鼠单次口服20mg/kg剂量的氯丙嗪氮氧化物的代谢情况进行了研究。2. 在尿液和粪便中鉴定出的代谢产物有氯丙嗪、7-羟基氯丙嗪、氯丙嗪亚砜、N-去甲基氯丙嗪和N-去甲基氯丙嗪亚砜。3. 在进行质谱分析之前,通过高效液相色谱法(h.p.l.c.)或气相色谱法(g.l.c.)分离代谢产物。通过将它们的质谱和色谱行为与 authentic 化合物的质谱和色谱行为直接比较,确定了代谢产物的结构。4. 在任何提取物中均未鉴定出氯丙嗪氮氧化物和任何保留完整氮氧化物功能的代谢产物,如氯丙嗪N,S-二氧化物。5. 在相同条件下给予3H-氯丙嗪氮氧化物时,粪便中排泄的放射性(52.1±9.7%)约为尿液中(26.9±7.2%)的两倍。

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