Characterization of the Phase II metabolites of rutaecarpine in rat by liquid chromatography-electrospray ionization-tandem mass spectrometry.
From the authors' previous studies on the Phase I metabolism of rutaecarpine, nine metabolites formed were identified as products of hydroxylation on the aromatic rings in rat liver microsomes. In order to determine the possible metabolic fate of rutaecarpine, the Phase II metabolites of rutaecarpine were characterized in the present study by using liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS). When male Sprague-Dawley rats were treated intravenously with 4 mg kg(-1) rutaecarpine, 16 different Phase I and II metabolites were identified in urine including four sulfate and four glucuronide conjugates. Phase I metabolites of rutaecarpine were identified as four mono-hydroxylated metabolites (M2-5) and four isobaric di-hydroxylated metabolites (M6-9). These metabolites were identical to the in vitro metabolites except one, which was hydroxylated in the aliphatic moiety. In addition, Phase II metabolites were identified as conjugated with sulfate (S1-4) and glucuronide (G1-4). In faeces, 11 different metabolites were identified. The metabolites M8 and glucuronide conjugated (G1-4) were not detected. Structures of all metabolites were confirmed with CID fragmentation spectra of MS(2), MS(3) and retention times by LC/ESI-MS.
Lee
S K
SK
College of Pharmacy, Yeungnam University, Gyeongsan, Korea.
Lee
D W
DW
Jeon
T W
TW
Jin
C H
CH
Kim
G H
GH
Jun
I H
IH
Lee
D J
DJ
Kim
S-I
SI
Kim
D-H
DH
Jahng
Y
Y
Jeong
T C
TC
D000470:Alkaloids / Q000378:metabolism* / Q000652:urine; D000818:Animals; D001646:Bile / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D020719:Glucuronides / Q000737:chemistry / Q000378:metabolism; D026121:Indole Alkaloids; D008297:Male; D011799:Quinazolines; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013431:Sulfates / Q000737:chemistry / Q000378:metabolism; D052999:Quinazolinones
D000470:Alkaloids; D020719:Glucuronides; D026121:Indole Alkaloids; D011799:Quinazolines; D013431:Sulfates; C028632:rutecarpine; D052999:Quinazolinones