[Study on the phase II metabolites of phenoprolamine hydrochloride in rat bile by LC/DAD/MSD].
OBJECTIVE
To study the phase II metabolites of phenoprolamine hydrochloride (DDPH) in rat bile.


METHODS
DDPH was administered by i.p. to bile duct-cannulated rats. Bile samples were collected before drug administration and up to 12 h after drug administration. After being purified and enriched with C-18 SPE columns the rat bile samples were analyzed by LC/DAD/MSD to identify the peaks of phase II metabolites. The fractions of phase II metabolites were prepared by HPLC and treated with beta-glucuronidase, and then were purified and enriched with C-18 SPE columns and analyzed by LC/DAD/MSD. The corresponding reference standards of DDPH phase I metabolites were analyzed by LC/DAD/MSD under identical conditions.


RESULTS
The peaks M7, M8 and M9 in the chromatograms of rat bile samples were the phase II metabolites of DDPH and the enzymatic hydrolysates of M7, M8 and M9 were 1-(2, 6-dimethyl-4-hydroxyphenoxy)-2-(3, 4-methoxyphenylethylamino)-propane (M3), 1-(2, 6-dimethyl-3-hydroxyphenoxy)-2-(3, 4-methoxyphenylethylamino)-propane (M2) and 1-(2,6-dimethylphenoxy)-2-(3-methoxy-4-hydroxyphenylethyl-amino)-propane (M1) respectively.


CONCLUSIONS
beta-1-O-[3,5-dimethyl-4-[-2-methyl-2-(3,4-dimethoxy-phenylethylamino)- ethoxy]-phenyl]-glucuronic acid (M7, glucuronide of M3), beta-1-O-[2, 4-dimethyl-3-[2-methyl-2-(3, 4-dimethoxy-phenylethylamino)-ethoxy]-phenyl]-glucuronic acid (M8, glucuronide of M2) and beta-1-O-[2-methoxy-4-[1-methyl-2-(2, 6-dimethylphenoxy)-ethylamino-ethyl]-phenyl]-glucuronic acid (M9, glucuronide of M1) were the phase II metabolites of DDPH in rat bile.
Ding
L
L
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China. dingli88@public1.ppt.js.cn
Zhang
Z X
ZX
Ni
P Z
PZ
Wang
G J
GJ
An
D K
DK
D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism* / Q000493:pharmacokinetics; D001646:Bile / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D020719:Glucuronides / Q000737:chemistry / Q000302:isolation & purification; D008297:Male; D010627:Phenethylamines / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization
C481914:1-O-(2,4-dimethyl-3-(2-methyl-2-(3,4-dimethoxyphenylethylamino)ethoxy)phenyl)glucuronic acid; D000959:Antihypertensive Agents; D020719:Glucuronides; D010627:Phenethylamines; C057485:1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane