Characterization of metabolites of clozapine N-oxide in the rat by micro-column high performance liquid chromatography mass spectrometry with electrospray interface
Characterization of metabolites of clozapine N-oxide in the rat by micro-column high performance liquid chromatography mass spectrometry with electrospray interface
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DOI：
10.1016/0731-7085(96)01738-4
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发表时间：
1996-08-01
影响因子：
3.4
通讯作者：
Midha, KK
中科院分区：
文献类型：
--
作者：
Lin, G;McKay, G;Midha, KK
研究了大鼠（n = 6）单次口服20 mg kg（-1）剂量后氯氮平N-氧化物的代谢。通过常规高效液相色谱法（HPLC）分离大鼠尿液的有机提取物，并通过微柱电喷雾HPLC/质谱法分析单个收集的馏分。在大鼠尿液中鉴别的化合物为氯氮平N-氧化物、氯氮平、N-去甲基氯氮平、8-去氯-8-羟基氯氮平、8-去氯-8-硫甲基氯氮平、N-去甲基氯氮平、8-去氯-8-羟基氯氮平; 8-去氯-8-硫甲基氯氮平、N-去甲基-8-去氯-8-硫甲基氯氮平和8-去氯-8-甲基亚磺酰基氯氮平。除原型氯氮平N-氧化物外，未发现其他含N-氧化物官能团的代谢产物。采用常规HPLC法和UV检测法测定大鼠尿液中排出的氯氮平N-氧化物、氯氮平和N-去甲基氯氮平的浓度。这三种分析物的回收率报告为0.24 h尿液中剂量的百分比，分别为0.93 +/-0.54%、0.06 +/- 0.03%和0.01 +/- 0.006%。
The metabolism of clozapine N-oxide was investigated in the rat (n = 6) after a single oral dose of 20 mg kg(-1). The organic extracts of rat urine were separated by conventional high performance liquid chromatography (HPLC) and individual collected fractions were analyzed by micro-column electrospray HPLC/mass spectroscopy. The compounds identified in rat urine were clozapine N-oxide, clozapine, N-desmethylclozapine, 8-deschloro-8-hydroxyclozapine, 8-deschloro-8-thiomethylclozapine, N-desmethylclozapine, 8-deschloro-8-hydroxpclozapine; 8-deschloro-8-thiomethylclozapine, N-desmethyl-8-deschloro-8-thiomethylclozapine and 8-deschloro-8-methylsulfinylclozapine. With the exception of the unchanged clozapine N-oxide, no other metabolite containing a N-oxide functional group could be found. the concentrations of clozapine N-oxide, clozapine and N-desmethylclozapine excreted from rat urine were determined utilizing a conventional HPLC procedure with UV detection. The recoveries of these three analytes reported as the percentage of the dosage from the 0.24 h urine are 0.93 +/- 0.54%, 0.06 +/- 0.03% and 0.01 +/- 0.006% respectively.