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РЖ ВИНИТИ 34 (BI48) 96.09-04Т1.132

He, H.
Phase I and II metabolites of benztropine in rat urine and bile [Text] / H. He, G. Mckay, K. K. Midha // Xenobiotica. - 1995. - Vol. 25, N 8. - P857-872 . - ISSN 0049-8254
Перевод заглавия: I и II фазы метаболизма бензтропина в моче и желчи крыс
Аннотация: Following oral administration of benztropine (10 mg/kg, body weight), the phase I metabolites, benztropine N-oxide, N-desmethylbenztropine, tropine, 4'-hydroxybenztropine, N-desmethyl-4'-hydroxybenztropine, 4'-hydroxybenztropine N-oxide and methoxy-4'-hydroxybenztropine, together with unmetabolized benztropine, were isolated and identified in rat urine and bile by GC-electron impact mass spectrometry (EI GC/MS), microcolumn LC-electrospray mass spectrometry (ES LC/MS) and HPLC followed by MS analysis. The mass spectra and chromatographic properties of isolated N-desmethylbenztropine, benztropine N-oxide and tropine were confirmed by comparison with authentic reference standards. Sufficient quantities of 4'-hydroxybenztropine and N-desmethyl-4'-hydroxybenztropine were isolated from the urine by tlc and examined by {1}H-nmr, ES/MS and EI/MS. The structure of the methoxy-4'-hydroxybenztropine metabolite was determined by EI/MS. 4'-Hydroxybenztropine N-oxide was identified by reacting it with a reducing agent, titanous chloride, to form 4'-hydroxybenztropine, which was then confirmed by comparing its EI/MS and ES/MS behaviour with a previously isolated and {1}H-nmrauthenticated sample. In addition, four intact glucuronide conjugates of benztropine were also characterized in bile and urine as phase II metabolites, including 4'-O-glucuronylbenzotropine, N-desmethyl-4'-O-glucuronylbenztropine, methoxy-4'-O-glucuronylbenzotropine, and 4'-O-glucuronylbenztropine N-oxide by hplc followed by ES/MS analysis. These results provide the first direct evidence of the precence of these metabolites of benztropine in rat. Канада, Col. Med., Univ. Saskatchewan, Saskatchewan S7N 5C9. Библ. 23

ГРНТИ	34.45.15

ВИНИТИ 341.45.15.09.39
Рубрики: БЕНЗТРОПИН
МЕТАБОЛИЗМ
ТРОПИН
ДЕЗМЕТИЛТРОПИН
ГИДРОКСИБЕНЗТРОПИН
ОБРАЗОВАНИЕ
МОЧА
ЖЕЛЧЬ
КРЫСЫ

Доп.точки доступа:
Mckay, G.; Midha, K.K.

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