Analysis of carnosic acid metabolites in rats by UHPLC-Q-Exactive MS

LOU Tian-yu1 MA Bei-bei1 LIANG Yao-yue1 WANG Chen-xiao1 LIU Jin-hui1 LI Rui-ji1 YU Shang-yue1 WANG Zhi-bin2

(1.School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China 100102)
(2.Beijing Institution of Tongrentang, Beijing, China 100079)

【Abstract】A method of ultra-high performance liquid chromatography coupled with quadrupole/electrostatic field Orbitrap high-resolution mass spectrometry (UHPLC-Q-Exactive MS) was established to comprehensively identify the metabolites of carnosic acid in rats. After oral gavage of carnosic acid CMC-Na suspension in rats, the urine, plasma, and feces samples were collected and pretreated by solid-phase extraction (SPE). Acquity UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm) was used with 0.1% formic acid solution (A)-acetonitrile (B) as the mobile phase for gradient elution. The biological samples were analyzed by quadrupole/electrostatic field Orbitrap high-resolution mass spectrometry in positive and negative ion modes. Based on the accurate molecular mass, fragment ion information, and related literature reports, a total of 28 compounds (including carnosic acid) were finally identified in rat samples. As a result, the main metabolic pathways of carnosic acid in rats are oxidation, hydroxylation, methylation, glucuronide conjugation, sulfate conjugation, S-cysteine conjugation, glutathione conjugation, demethylation, decarbonylation, and their composite reactions. The study showed that the metabolism of carnosic acid in rats could be efficiently and comprehensively elucidated by using UHPLC-Q-Exactive MS, providing a reference for clarifying the material basis and metabolic mechanism of carnosic acid.

【Keywords】 carnosic acid; UHPLC-Q-Exactive MS; metabolites; metabolic pathways;

【DOI】

【Funds】 Chinese Pharmacopoeia Commission Project (12) Project of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica (JKLPSE201816) Project of Shanxi Key Laboratory for Encephalology of Traditional Chinese Medicine (Shanxi University of Chinese Medicine) (CME-OP-2017002)

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This Article

ISSN:1001-5302

CN:11-2272/R

Vol 45, No. 16, Pages 3952-3960

August 2020

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Article Outline

Abstract

  • 1 Materials
  • 2 Methods
  • 3 Results
  • 4 Discussion
  • References