鉴定大鼠注射绿原酸后体内的代谢产物

绿原酸为多种中药注射液的主要成分, 本文采用超高效液相色谱-四极杆飞行时间质谱法 (UPLC/Q- TOF MS) 鉴定大鼠注射给予绿原酸后胆汁、尿、粪和血浆中的代谢产物。利用碰撞能量梯度 (MS^E) 和质量亏损过滤 (MDF) 技术, 在大鼠胆汁、尿、粪和血浆中共检测到35种代谢产物。胆汁中主要代谢产物为O-甲基绿原酸谷胱甘肽结合物, 其排泄量超过胆汁中全部代谢物的80%, 尿中主要为原形、O-甲基结合物、水解代谢产物及葡糖醛酸结合物, 粪中主要为O-甲基结合物及其半胱氨酸结合物, 血浆中主要为原形化合物。绿原酸及其代谢产物经尿和粪便排泄比例相近。实验结果表明, 绿原酸在大鼠体内代谢广泛, 主要途径之一是与谷胱甘肽结合, 提示绿原酸的烯酮双键具有亲电性, 可能与蛋白的巯基共价结合, 导致过敏性不良反应, 应予以关注。

Metabolites of injected chlorogenic acid in rats

Chlorogenic acid (5-CQA) is one of the major components in some Chinese herbal injections.  However, the metabolism of 5-CQA in rats after intravenous injection has not been determined.  An ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) method was applied to identify the metabolites in bile, urine, feces and plasma after a single intravenous administration of 10 mg·kg⁻¹ 5-CQA to rats. Using MS^E and mass defect filter techniques, a total of 35 metabolites were detected in bile, urine, feces and plasma.  The predominant metabolites in bile were glutathione conjugates of O-methyl- 5-CQA, accounting for approximately 80% of the metabolites excreted in bile.  The major components in urine were parent drug, O-methyl-5-CQA, hydrolyzed metabolites and glucuronide conjugates.  The major components in feces were O-methyl-5-CQA and its cysteine conjugates.  The major component in plasma was the parent drug.  The urinary and fecal excretion pathways were equally important to 5-CQA in rats.  These results demonstrate that 5-CQA undergoes extensively metabolism in rats and are highly reactive to nucleophiles such as GSH.  This finding indicates that attention should be paid on the injections containing 5-CQA, which may covalently bind to proteins, leading to allergenic drug reactions.