Metabolites of 1-(1-(6-methoxyl-2-naphthyl)ethyl)-2-(4-nitrobenzyl)-6,7-dimethoxyl-1,2,3,4-tetrahydroisoquinoline hydrobromide in rat by LC-MS/MS method.
- Author:
Lei-na WANG
1
;
Min SONG
;
Tai-jun HANG
;
Zheng-xing ZHANG
Author Information
1. Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Bile;
metabolism;
Chromatography, Liquid;
Female;
Fibrinolytic Agents;
blood;
metabolism;
pharmacokinetics;
urine;
Male;
Rats;
Rats, Sprague-Dawley;
Spectrometry, Mass, Electrospray Ionization;
Tetrahydroisoquinolines;
blood;
metabolism;
pharmacokinetics;
urine
- From:
Acta Pharmaceutica Sinica
2007;42(11):1176-1182
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the principal metabolites of 1-(1-(6-methoxyl-2-naphthyl) ethyl)-2-(4-nitrobenzyl)-6,7-dimethoxyl-1,2,3,4-tetrahydroisoquinoline hydrobromide (code designation: P91024) in rats after ig administration by LC-MS/MS, the phase I metabolites were discovered by comparing the fullscan and SIM chromatograms of the test samples with the corresponding blanks. The structures of phase I metabolites were identified by ESI-MS spectra and the product spectra of the corresponding adduct ions. The phase II metabolites were identified in the test samples after the phase I metabolites were completely removed with solvent extraction and then treated with glucuronidase for enzymolysis of phase II glucuronide conjugates and the hydrolysates. Two phase I metabolites of P91024 were identified in rat feces, one phase I and five phase II in bile, one phase I and three phase II in urine, and four phase I and one phase II in plasma. Their structures were elucidated, separately. P91024 was extensively metabolized in rat. The metabolites can be easily screened and identified by LC-MS/MS method.