[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].
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.
Wang
Lei-na
LN
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Song
Min
M
Hang
Tai-jun
TJ
Zhang
Zheng-xing
ZX
D000818:Animals; D001646:Bile / Q000378:metabolism*; D002853:Chromatography, Liquid; D005260:Female; D005343:Fibrinolytic Agents / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D044005:Tetrahydroisoquinolines / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine
D005343:Fibrinolytic Agents; C542583:P91024; D044005:Tetrahydroisoquinolines