Characterization of the Phase II metabolites of rutaecarpine in rat by liquid chromatography-electrospray ionization-tandem mass spectrometry

Abstract

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.

Effects of rutaecarpine on the metabolism and urinary excretion of caffeine in rats

“…The dried unripe fruit of Evodia rutaecarpa has traditionally been used as a remedy for gastrointestinal disorders, headache, amenorrhea, and postpartum hemorrhage (Ueng et al, 2002;Lee et al, 2004a). Rutaecarpine is an excellent example of a biologically active constituent from natural resources, not only because it induces some CYP enzymes, but also because its metabolic pathway, including phases 1 and 2, has clearly been characterized (Lee et al, 2004a(Lee et al, , 2004b(Lee et al, , 2005Jan et al, 2005). As shown in previous studies, rutaecarpine induces the activity of hepatic CYPs (Ueng et al, 2001(Ueng et al, , 2002Lee et al, 2004a).…”

Progress in the Studies on Rutaecarpine

“…In vivo phase I studies on male Sprague-Dawley rats were also pursued to give four mono-hydroxylated metabolites such as 3-hydroxyrutaecarpine (M5, 10.1%), 9-hydroxyrutaecarpine (M4, 7.2%), 10-hydroxyrutaecarpine (M2, 24.6%) and 11-hydroxyrutaecarpine (M3, 58.1%) and 4 isobaric di-hydroxylated metabolites (M7-M10) (Figure 1) in urine [97], which were identical to the in vitro metabolites except one (M1) that was hydroxylated in the aliphatic moiety. On the other hand, in faeces, the distribution of monohydroxylated metabolites were somewhat different from those in urine.…”

“…From the urine of male Sprague-Dawley rats, pretreated intravenously with rutaecarpine, 16 different phase I and II metabolites were identified including four sulfate and four glucuronide conjugates (Figure 3) [97]. Phase I metabolites of rutaecarpine were identified as four mono-hydroxylated rutaecarpines and four isobaric di-hydroxylated rutaecarpines as metabolites ( vide ante ).…”

Metabolism of FPP-3, an Anti-inflammatory Propenone Compound, in Rat by Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry

“…2, because the ion at m/z 186 formed by the loss of H 2 O from the protonated M2 at m/z 204 might be more stable than the ion at m/z 204. 4,8,9) Glucuronidation, catalyzed by endoplasmic reticulumbound UDP-glucuronosyl-transferases, represents an important pathway for the elimination of xenobiotics and endogenous compounds in mammalians. 10) Interestingly, only a small amount of glucuronide conjugates were detected in bile in the present study.…”