Premium
Biotransformation of terodiline I. Identification of metabolites in dog urine by mass spectrometry
Author(s) -
Norén Bengt,
Strōmberg Signhild,
Ericsson Ōrjan,
Olsson LarsInge,
Moses Pinchas
Publication year - 1985
Publication title -
biomedical mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 0306-042X
DOI - 10.1002/bms.1200120804
Subject(s) - metabolite , chemistry , hydroxylation , hydroxymethyl , mephenytoin , stereochemistry , butylamine , biotransformation , medicinal chemistry , organic chemistry , amine gas treating , biochemistry , enzyme , cytochrome p450 , cyp2c19
Nine metabolites of terodiline ( N‐tert ‐butyl‐4,4‐diphenyl‐2‐butylamine) have been identified in dog urine by various chromatographic techniques and mass spectrometry. The main metabolic pathway is aromatic hydroxylation, leading to the quantitatively most important metabolite, N‐tert ‐butyl‐4‐(4‐hydroxyphenyl)‐4‐phenyl‐2‐butylamine, and to two dihydroxylated metabolites, one mono substituted in both rings ( N‐tert ‐butyl‐4,4′‐bis(4‐hydroxyphenyl)‐2‐butylamine), and one disubstituted in one ring ( N‐tert ‐butyl‐4‐(3,4‐dihydroxyphenyl)‐4‐phenyl‐2‐butylamine). The latter is further metabolized by methylation, forming N‐tert ‐butyl‐4‐(4‐hydroxy‐3‐methoxyphenyl)‐4‐phenyl‐2‐butylamine, the second most abundant metabolite. Still another metabolite is formed by hydroxylation in the tert ‐butyl group to N ‐(2‐hydroxymethyl‐2‐propyl)‐4,4‐diphenyl‐2‐butylamine. A very minor dihydroxylated metabolite results from oxidation both in an aromatic ring and in the tert ‐butyl group, giving N ‐(2‐hydroxymethyl‐2‐propyl)‐4‐(4‐hydroxyphenyl)‐4‐phenyl‐2‐butylamine. Oxidation of the carbon adjacent to the nitrogen and subsequent deamination gives the two ketones 4‐(4‐hydroxyphenyl)‐4‐phenyl‐2‐butanone and 4‐(4‐hydroxy‐3‐methoxyphenyl)‐4‐phenyl‐2‐butanone. Reduction of the carbonyl function in the former yields the corresponding alcohol, 4‐(4‐hydroxyphenyl)‐4‐phenyl‐2‐butanol. Some unchanged terodiline is also present. All metabolites formed by functionalization appear to be extensively conjugated, presumably with glucuronic acid.