Characterization of metabolites of clozapine N-oxide in the rat by micro-column high performance liquid chromatography/mass spectrometry with electrospray interface

✍ Scribed by G. Lin; G. McKay; K.K. Midha

• Book ID: 103912549
• Publisher: Elsevier Science
• Year: 1996
• Tongue: English
• Weight: 954 KB
• Volume: 14
• Category: Article
• ISSN: 0731-7085
• DOI: 10.1016/0731-7085(96)01738-4

✦ Synopsis

The metabolism of clozapine N-oxide was investigated in the rat (n = 6) after a single oral dose of 20 mg kg i. 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.