Characterization of metabolites of clozapine N-oxide in the rat by micro-column high performance liquid chromatography/mass spectrometry with electrospray interface.
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.
Lin
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G
Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
McKay
G
G
Midha
K K
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D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003024:Clozapine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D005260:Female; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011917:Rats, Inbred Lew
C058272:norclozapine; D003024:Clozapine; C079149:clozapine N-oxide