Identification of urinary metabolites of clemastine after oral administration to man.
The metabolism of clemastine, 2-[2-[1-(4-chlorophenyl)-1-phenylethoxylethyl])-1-methylpyrrolidin e, has been studied in three adult male volunteers after a single oral dose of 20 mg as the fumarate. After enzymatic hydrolysis solvent extracts of urine were derivatized with N-methyl-N-trimethylsilyltrifluoroacetamide-ammonium iodide and analysed by gas chromatography-mass spectrometry. The structures of metabolites were determined on the basis of electron impact and chemical ionization mass spectra and the identities of some (e.g. carbinol, 4-chlorobenzophenone and 4-chlorophenylstyrene) were confirmed by use of authentic standards. The principal route of metabolism of clemastine in man involves direct oxidation, O-dealkylation (fission of the ether bond), aromatic hydroxylation, aliphatic oxidation, alcoholic dehydration, and then enzymatic hydrolysis. Of the total amount of metabolites excreted in the urine 35% was carbinol (metabolite M3, major metabolite), 15% was M1, 17% was M2, 11% was M4, 9% was M5, 8% was M6 and 5% was M7.
Choi
M H
MH
Bioanalysis and Biotransformation Research Center, Korea Institute of Science & Technology, Seoul.
Jung
B H
BH
Chung
B C
BC
D000081:Acetamides; D000328:Adult; D002974:Clemastine / Q000378:metabolism* / Q000652:urine; D005463:Fluoroacetates; D008401:Gas Chromatography-Mass Spectrometry / Q000295:instrumentation / Q000379:methods; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry*; D008297:Male; D000432:Methanol / Q000652:urine; D014269:Trifluoroacetic Acid / Q000737:chemistry; D014297:Trimethylsilyl Compounds / Q000737:chemistry*
D000081:Acetamides; D005463:Fluoroacetates; D007202:Indicators and Reagents; D014297:Trimethylsilyl Compounds; C086665:N-methyl-N-(trimethylsilyl)trifluoroacetamide; D002974:Clemastine; D014269:Trifluoroacetic Acid; D000432:Methanol