Characterization of new metabolites from in vivo biotransformation of norisoboldine by liquid chromatography/mass spectrometry and NMR spectroscopy.
Norisoboldine (1,9-dihydroxy-2,10-dimethoxynoraporphine) is one of the major bioactive isoquinoline alkaloids in Linderae radix, a commonly used Chinese herbal medicine. The aim of this study is to isolate and characterize metabolites of norisoboldine after gavage feeding in rats. High-performance liquid chromatography coupled with electrospray ionization and ion-trap mass spectrometry (HPLC-ESI/MS(n)) was used to identify metabolites of norisoboldine in rat urine and bile samples. A total of five metabolites of norisoboldine were characterized by comparing retention time and UV absorption in HPLC, and by molecular mass and fragmentation pattern of the analytes by mass spectrometry with those of norisoboldine. Two new glucuronide conjugates of norisoboldine, noriosboldine-1-O-beta-D-glucuronide and norisoboldine-9-O-alpha-D-glucuronide, were isolated from rat urine samples and their structures were confirmed by NMR spectroscopy ((1)H, (13)C, HMBC and HSQC) for the first time. The results suggested that glucuronidation and sulfation were involved in metabolic pathways of norisoboldine in rat.
Chen
Jian-Zhong
JZ
Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210038, China.
Chou
Gui-Xin
GX
Wang
Chang-Hong
CH
Yang
Li
L
Bligh
S W Annie
SW
Wang
Zheng-Tao
ZT
D000470:Alkaloids / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013056:Spectrophotometry, Ultraviolet
D000470:Alkaloids; C464745:norisoboldine