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In vitro metabolism of corydaline in human liver microsomes and hepatocytes using liquid chromatography‐ion trap mass spectrometry
Author(s) -
Ji Hye Young,
Lee Hyeri,
Kim JeongHan,
Kim Ki Hyun,
Lee Kang Ro,
Shim Hyun Joo,
Son Miwon,
Lee Hye Suk
Publication year - 2012
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.201101094
Subject(s) - microsome , chemistry , chromatography , hydroxylation , mass spectrometry , metabolism , metabolic pathway , metabolite , s9 fraction , incubation , in vitro , ion trap , drug metabolism , biochemistry , enzyme
Corydaline is a pharmacologically active isoquinoline alkaloid isolated from C orydalis t ubers. It exhibits the antiacetylcholinesterase, antiallergic, antinociceptive, and gastric emptying activities. The purposes of this study were to establish in vitro metabolic pathways of corydaline in human liver microsomes and hepatocytes by identification of their metabolites using liquid chromatography‐ion trap mass spectrometry. Human liver microsomal incubation of corydaline in the presence of an NADPH ‐generating system resulted in the formation of nine metabolites, namely, four O ‐desmethylcorydaline [ M 1 (yuanhunine), M 2 (9‐ O ‐desmethylcorydaline), M 3 (isocorybulbine), and M 4 (corybulbine)], three di‐ O ‐desmethylcorydaline [ M 5 (9,10‐di‐ O ‐desmethylcorydaline), M 6 (2,10‐di‐ O ‐desmethylcorydaline), and M 7 (3,10‐di‐ O ‐desmethylcorydaline)], M 8 (hydroxyyuanhunine), and M 9 (hydroxycorydaline). Incubation of corydaline in human hepatocytes produced four metabolites including M 1, M 5, M 6, and M 9. O ‐Demethylation and hydroxylation were the major metabolic pathways for the metabolism of corydaline in human liver microsomes and hepatocytes.