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J Pharm Biomed Anal. 1996 Aug;14(11):1561-77.

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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Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T., Hong Kong.


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-hydroxyclozapine, 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.

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