Phase I and phase II metabolite identification of rutaecarpine in freshly isolated hepatocytes from male Sprague–Dawley rats

Abstract

Rutaecarpine, an alkaloid originally isolated from Evodia rutaecarpa, has been used for the treatment of gastrointestinal disorders in Asia. In the present study, the phase I and phase II metabolites of rutaecarpine were investigated in freshly isolated hepatocytes from male Sprague-Dawley rats. The individual metabolites were characterized via liquid chromatography-tandem mass spectrometry. The incubation of rutaecarpine with freshly isolated hepatocytes for 2 h yielded five major phase I metabolites. In addition, three glucuronide conjugates and four sulfate conjugates were observed. Because the majority of metabolites observed in vivo were identified, freshly isolated hepatocytes might be useful for the identification of certain metabolites formed from drug candidates from a reduced number of experimental animals.

Characterization of the in Vitro Metabolic Profile of Evodiamine in Human Liver Microsomes and Hepatocytes by UHPLC-Q Exactive Mass Spectrometer

“…M10 was tentatively proposed as glucuronide conjugate of M9. This metabolic pathway was similar to that of rutaecarpine, an analog of evodiamine ( Lee et al, 2017 ).…”

“…There are several literatures regarding metabolism of alkaloids from E. rutaecarpa ( Li et al, 2006 ; Wen et al, 2014 ; Lee et al, 2017 ). Due the lack of references, the major metabolic sites were not assigned.…”

“…Previous pharmacokinetic study demonstrated that evodiamine showed very low oral bioavailability ( Komatsu et al, 1993 ), which may be attributed to the extensive metabolism. Komatsu et al (1993) have reported that evodiamine could be rapidly converted to its metabolites (see also Lee et al, 2017 ), and its metabolite 10-hydroxyevodiamine showed stronger cytotoxicity than evodiamine ( Li et al, 2006 ). Wen et al (2014) reported that evodiamine undergo metabolic bioactivation to form its reactive metabolites, and evodiamine is a time-dependent inhibitor of CYP3A4.…”

Pharmacokinetic, metabolic profiling and elimination of brusatol in rats

“…The CD software gave the possible metabolic pathway of each metabolite. The MS 2 spectrum and the Mass Frontier software were used for further analysis and predicted the structures of metabolites according to the known common metabolic pathways (Lee et al, 2017). The MS 2 spectrum, possible fragments and mechanisms of brusatol and its metabolites are shown in Figure 5.…”

Synthesis, Antitumor Activity, Oil-Water Partition Coefficient, and Theoretical Calculation of 2 New Rutaecarpine Derivatives With Methoxy Groups

“…9,10 Structural modification of RUT with active groups, like -OH, -OCH 3 , or -Br could solve this problem. [10][11][12][13] The methoxy (-OCH 3 ) and hydroxyl (-OH) groups are widely used due to their powerful biological activity, 11,[14][15][16] for example, hortiacine with 1 methoxy at 10, euxylophoricine A with 2 methoxy at 2 and 3 positions. Generally, RUT has been structurally modified at 3, 11, and 12 positions, 15 and the 2 position and 10 position derivatives of RUT have been reported rarely.…”