Metabolic Profile of Isocorynoxeine in Rats Obtained by Ultra-High Performance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry

Abstract

The result indicates that IC undergoes extensive metabolism in vivo, mainly including hydrolysis, oxidation, isomerization, demethylation, epoxidation, reduction, glucuronidation, hydroxylation and N-oxidation, which is helpful for the further pharmacokinetic study of IC in vivo.

Identification of the absorbed components and their metabolites of Tianma‐Gouteng granule in rat plasma and bile using ultra‐high‐performance liquid chromatography combined with quadrupole time‐of‐flight mass spectrometry

“…M19 was tentatively identified as a reduction and demethylation metabolite of GM (P27) or HTE (P28). According to our previous studies (Qi et al, ; Zhao et al, ), we also found that ICO (P15) and COR (P17) could be converted into IRN (P16) and RIN (P19) by a reduction reaction in vivo , respectively. However, none of the epoxidation and N ‐oxidation metabolites of ICO were found in this study.…”

“…M13 (retention time, t R 4.14 min), M16 ( t R 5.15 min), M18 ( t R 5.61 min) and M23 ( t R 6.19 min) exhibited the [M + H] + ions at m/z 369.1839, 369.1839, 369.1799, 369.1799 with the same molecular formula, speculated to be C 21 H 24 N 2 O 4 , and they were 14 Da (‐CH 2 ) lower than that of ICO (P15) or COR (P17). Comparing the retention time, accurate mass and diagnostic fragment ions with those of our previous studies (Yuan et al, ; Zhao et al, ), M13, M16, M18 and M23 were tentatively identified as isocorynoxeinic acid, 18,19‐dehydrocorynoxinic acid, corynoxeinic acid and 18,19‐dehydrocorynoxinic acid B, respectively, which were hydrolyzed metabolites of ICO (P15) or COR (P17). When identifying the tetracyclic oxindole alkaloids possessing a 7S configuration, there were two diagnostic fragmentation ions, m/z 201 (C 12 H 13 N 2 O) and 187 (C 11 H 11 N 2 O), which were reported in our previous studies (Qi, Chen, Sun, Simpkins, & Yuan, ; Zhao et al, ).…”

“…It was also found that some alkaloid components were excreted by bile mainly in the forms of the glucuronidated metabolites. M1, M3, M4, M10 and M12 were glucuronides of alkaloids from Uncariae Ramulus Cum Uncis and Leonuri Herba (Qi et al, ; Zhao et al, ; Zhu et al, ). An anthraquinone (P24) and its four related metabolites (M20, M22, M24 and M30) and a stilbene (P11) and its four related metabolites (M2, M6, M9 and M17) were identified in bile.…”

“…It is necessary to provide an integrated absorbed and metabolic profile for a scientific understanding of the therapeutic effects as well as theories about TCM formulations. At present, researchers are still focusing on the individual chemical composition and herbs of TGG in vivo (Du et al, ; Huang et al, ; Tang et al, ; Zhao, Qi, Chen, Sun, & Yuan, ). However, to the best of our knowledge, based on overall and systematic experiments, there have been few reports on the absorbed prototype components and the metabolites of TGG.…”

Pharmacokinetics of isocorynoxeine in rat plasma after intraperitoneal administration by UPLC–MS/MS

“…Although the pharmacokinetic characteristics of isocorynoxeine given by oral administration in rat had been revealed in recent years, no study on the i.p. administration in vivo until now has been investigated [18,19]. In order to further understand the absorption and distribution of isocorynoxeine by i.p.…”