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[Study on the phase II metabolites of phenoprolamine hydrochloride in rat bile by LC/DAD/MSD]
1Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China. dingli88@public1.ppt.js.cn
Aim:
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.
Conclusion:
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.
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