TY - JOUR T1 - Isolation and Identification of Clozapine Metabolites in Patient Urine JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 923 LP - 931 VL - 29 IS - 6 AU - Gisela Schaber AU - Gerlinde Wiatr AU - Helmut Wachsmuth AU - Markus Dachtler AU - Klaus Albert AU - Ines Gaertner AU - Ursula Breyer-Pfaff Y1 - 2001/06/01 UR - http://dmd.aspetjournals.org/content/29/6/923.abstract N2 - Biotransformation products of the atypical neuroleptic clozapine were isolated from urine samples of three schizophrenic patients by solid-phase extraction, liquid-liquid extraction for the separation of unpolar and polar metabolites, and thin-layer chromatography followed by final purification by high-performance liquid chromatography. Their structures were elucidated by mass spectrometry and1H NMR spectroscopy and in some cases by enzymatic deconjugation. Besides the known metabolites desmethylclozapine, clozapine N-oxide, 8-deschloro-8-hydroxyclozapine, and 8-deschloro-8-hydroxydesmethylclozapine, the unpolar fraction contained 7-hydroxyclozapine and a compound in which the piperazine ring of clozapine was partially degraded to an ethylenediamine derivative. Novel metabolites identified in the polar fraction were the sulfate and glucuronide conjugates of 7-hydroxyclozapineN-oxide, 8-deschloro-8-hydroxyclozapine-O-glucuronide, and theO-glucuronide ofN-hydroxydesmethylclozapine; further conjugates were tentatively identified as 9-hydroxydesmethylclozapine-O-sulfate and 6-hydroxyclozapine-O-sulfate. In addition, the previously described conjugates 7-hydroxydesmethylclozapine-O-sulfate, 7-hydroxyclozapine-O-glucuronide and -O-sulfate, 8-deschloro-8-hydroxydesmethylclozapine-O-glucuronide, and the quaternary ammonium glucuronide of clozapine were detected. The American Society for Pharmacology and Experimental Therapeutics ER -