N-dephenylated and N-phenyl urinary metabolites of mociprazine (CERM 3517) in beagle dogs after oral administration. A mass spectrometric determination.
CERM 3517 (mociprazine), a new anti-emetic compound, was administered orally to six beagle dogs at 10 mg/kg b.i.d. for four days. Unconjugated urinary metabolites were identified by GC-MS analysis against synthesized reference compounds, after solvent extraction, purification by TLC and concentration. Twenty one metabolites were identified indicating the following biotransformations: N-dephenylation followed by reactions on the exposed secondary amine such as methylation acetylation; and parahydroxylation on the phenyl ring, and monohyrdoxylation on the cyclohexyl ring in different positions. The parahydroxylation on the phenyl ring was confirmed by NMR analysis. Some reactions on the secondary amine were unexpected, such as N-formylation. N-dephenylation and N-formylation were confirmed not to be artifacts. The role of the para-hydroxyl intermediate was proved to be essential for the N-dephenylation after intravenous administration of meta- and para-hydroxylated derivatives of CERM 3517 to five beagle dogs.
Groupe de Recherches en Biodynamique du médicament, Laboratoire de Chimie analytique, Clermont-Ferrand, France.
A
A
Enreille
J F
JF
Pognat
M J
MJ
Galmier
C
C
Lartigue-Mattei
J L
JL
Chabard
N
N
Busch
J A
JA
Berger
D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D002855:Chromatography, Thin Layer; D004285:Dogs; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006900:Hydroxylation; D007477:Ions; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D010879:Piperazines / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine
D000932:Antiemetics; D007477:Ions; D010879:Piperazines; C048371:mociprazine