LC/DAD/MSD技术研究大鼠服药胆汁中盐酸非洛普I相代谢产物

STUDY ON THE PHASE I METABOLITES OF PHONEPROLAMINE HYDROCHLORIDE IN RAT BILE BY LC/DAD/MSD

目的 研究大鼠服药后胆汁中盐酸非洛普 (DDPH)I相代谢物。方法 大鼠做胆管插管 ,分别收集ipDDPH之前的空白胆汁及服药后 12h内的服药胆汁 ,将大鼠胆汁以葡糖醛酸酶水解后进C 18SPE小柱进行纯化富集 ,再进行LC/DAD/MSD分析 ;同时将合成的 6个DDPH模拟代谢物M1-M6的对照品混合液按相同条件进行LC/DAD/MSD分析对照。结果 大鼠服药胆汁色谱图中峰A ,B ,C ,D ,E和F分别与M1,M2 ,M3,M5,M4 和M6的保留时间、紫外吸收光谱、分子量及碎片离子完全一致。结论 M1,M2 ,M3,M4 。

AIM To study the phase I metabolites of phenoprolamine hydrochloride (DDPH) in rat bile. METHODS DDPH was administered ip to bile duct cannulated rats. Bile samples were collected before administration and up to 12 h after administration. After being treated with β 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 (M 1), 1 (2,6 dimethyl 3 hydroxyphenoxy) 2 (3,4 methoxy phenylethylamino) propane (M 2), 1 (2,6 dimethyl 4 hydroxyphenoxy) 2 (3,4 methoxyphenylethylamino) propane (M 3), 1 (2,6 dimethyl 4 hydroxyphenoxy) 2 (3 hydroxy 4 methoxyphenylethylamino) propane (M 4), 1 (2,6 dimethyl 3 hydroxyphenoxy) 2 (3 hydroxy 4 methoxyphenylethylamino) propane (M 5) and 1 (2,6 dimethyl 4 hydroxyphenoxy) 2 (3 methoxy 4 hydroxyphenylethylamino) propane (M 6) were analyzed by LC/DAD/MSD under identical conditions. RESULTS 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 M 1, M 2, M 3, M 5, M 4 and M 6, respectively. CONCLUSION M 1, M 2, M 3, M 4, M 5 and M 6 were identified as the phase I metabolites of DDPH in the rat.