title: [Metabolites of injected chlorogenic acid in rats].
abstract: 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 x kg(-1) 5-CQA to rats. Using MSE 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.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Cen
authors.initials: C
authors.lastname: Xie
authors.forename: Da-Fang
authors.initials: DF
authors.lastname: Zhong
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Chen
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002726:Chlorogenic Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003545:Cysteine / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D020719:Glucuronides / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D020719:Glucuronides; D002726:Chlorogenic Acid; D005978:Glutathione; D003545:Cysteine