The main metabolites of loxoprofen sodium were isolated from rat urine by column chromatography. Their chemical structures were determined on the basis of spectral data and by comparison of the metabolites with authentic samples to be as follows : the parent acid (M-0), two reduction products, i.e., the cis-alcohol (M-1) and the trans-alcohol (M-2), the α-hydroxy ketone (M-3) and three diol metabolites (M-4, M-5 and M-6). The established metabolite structures all indicated that metabolic reactions of loxoprofen in rats occur only at the cyclopentanone moiety. The trans-alcohol metabolite, which has a high inhibitory activity on prostaglandin (PG)-synthetase, was determined to be optically pure, with (2S, 1'R, 2'S)-configurations, by high performance liquid chromatography (HPLC) analysis after derivatization to the diastereomeric amide of the carboxy group with (-)-α-phenylethylamine reagent, and subsequently to the ester of the hydroxy function using (-)-α-methoxy-α-trifluoromethylphenylacetyl chloride.
通过柱色谱法从大鼠尿液中分离出
洛索洛芬钠的主要代谢产物。根据光谱数据以及将代谢产物与标准样品进行比较,确定了它们的
化学结构,具体如下:母体酸(M-0)、两种还原产物(即顺式醇(M-1)和反式醇(M-2))、α-羟基酮(M-3)以及三种二醇代谢产物(
M-4、M-5和M-6)。已确定的代谢产物结构均表明,
洛索洛芬在大鼠体内的代谢反应仅发生在
环戊酮部分。反式醇代谢产物对
前列腺素(
PG)合成酶具有高度抑制活性,经(-)-
α-苯乙胺试剂衍生为羧基的非对映酰胺,再使用(-)-α-甲氧基-α-三
氟甲基
苯乙酰氯衍生为羟基官能团的酯,通过高效
液相色谱(HPLC)分析确定其具有(2S, 1'R, 2'S)构象,为光学纯。