Identification of three sulfate-conjugated metabolites of berberine chloride in healthy volunteers' urine after oral administration.
OBJECTIVE
To identify the structure of unknown metabolites of berberine (Ber) in human urine after oral administration.


METHODS
Urine samples were obtained from 5 volunteers after they orally took Ber chloride 0.9 g per day for three days. Metabolites in urine samples were isolated and purified by polyporous resin column chromatography. The individual metabolites were identified mainly using electrospray ionization mass spectroscopy (ESI-MS) and proton nuclear magnetic resonance (1H NMR) spectroscopy.


RESULTS
Three unknown metabolites (M1, M2, and M3) were isolated. They were susceptible to arylsufatase. ESI-MS measurements of M1, M2, and M3 produced quasimolecular ions [M+H]+, m/z 17.9, 404.0, and 402.0 respectively. Especially, each of them produced a characteristic protonated ion [M-80+H]+, which can be ascribed as quasimolecular ions lost a SO3 fragment. 1H NMR spectra of the metabolites were also obtained and each of 1H signals was assigned.


CONCLUSIONS
Structures of M1, M2, and M3 were firmly identified as jatrorrhizine-3-sulfate, demethyleneberberine-2-sulfate, and thalifendine-10-sulfate, and the major metabolite was M2.
Pan
Jun-Fang
JF
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031,China.
Yu
Chen
C
Zhu
Da-Yuan
DY
Zhang
Hui
H
Zeng
Jia-Feng
JF
Jiang
Shan-Hao
SH
Ren
Jian-Ying
JY
D000328:Adult; D000930:Antidiarrheals / Q000378:metabolism / Q000652:urine; D001599:Berberine / Q000031:analogs & derivatives / Q000032:analysis* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D021241:Spectrometry, Mass, Electrospray Ionization; D013431:Sulfates / Q000378:metabolism*
D000930:Antidiarrheals; D013431:Sulfates; C055785:jatrorrhizine; D001599:Berberine; C477156:thalifendine; C477155:demethyleneberberine