[Study on the phase I metabolites of phenoprolamine hydrochloride in rat bile by LC/DAD/MSD]

To study the phase I metabolites of phenoprolamine hydrochloride (DDPH) in rat bile.

DDPH was administered i.p. to bile duct-cannulated rats. Bile samples were collected before administration and up to 12 h after administration. After being treated with beta-glucuronidase, the bile samples were purified and enriched with C-18 SPE columns, and then were analyzed by LC/DAD/MSD. The samples containing synthesized reference standards of DDPH metabolite 1-(2, 6-dimethylphenoxy)-2-(3-methoxy-4-hydroxyphenylethylamino)-propane (M1), 1-(2, 6-dimethyl-3-hydroxyphenoxy)-2-(3, 4-methoxy-phenylethylamino)-propane (M2), 1-(2,6-dimethyl-4-hydroxyphenoxy)-2-(3,4- methoxyphenylethylamino)-propane (M3), 1-(2, 6-dimethyl-3-hydroxyphenoxy)-2-(3-hydroxy-4- methoxyphenylethylamino)-propane (M4), 1-(2, 6-dimethyl-3-hydroxyphenoxy)-2- (3-hydroxy-4-methoxyphenylethylamino)-propane (M5) and 1-(2,6-dimethyl-4-hydroxyphenoxy)-2-(3-methoxy-4- hydroxyphenylethylamino)-propane (M6) were analyzed by LC/DAD/MSD under identical conditions.

The retention times, UV spectra, molecular weights and production spectra (obtained by collision-induced dissociation) of the apparent ions of peak A, B, C, D, E and F in the total ion chromatogram of DDPH treated rat bile sample were consistent with those of M1, M2, M3, M5, M4 and M6, respectively.

M1, M2, M3, M4, M5 and M6 were identified as the phase I metabolites of DDPH in the rat.