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.