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Analysis of NaoMaiTong Metabolites Using High-Performance Liquid Chromatography/High-Resolution Mass Spectrometry in Rat Urine

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Abstract

NaoMaiTong (NMT), consisting of Radix et Rhizoma Rhei, Radix Ginseng, Radix Puerariae, and Rhizoma Ligustici Chuanxiong, is widely used for treating ischemia cerebral apoplexy. In this work, a rapid high-performance liquid chromatograph coupled with a quadrupole-orbitrap mass spectrometer (HPLC-Q-Orbitrap) was developed for detection and identification of chemical compounds in rat urine after oral administration of NaoMaiTong and its single herbs. Using targeted screening and the mass defect filter of MetWorks™ software, a total of 157 ingredients were detected in the NaoMaiTong drug-containing group within 36 h, including 70 prototype chemicals and 61 related metabolites that were unambiguously discriminated. There were anthraquinones, triterpenoid saponins, isoflavones, puerosides, phthalides, phenolic acid, etc. Twelve triterpenoid saponins, including 7 metabolites, were first discovered in rat urine after administration. Mirificin-Glc and methoxypuerarin were first discovered in the Radix Puerariae. The results indicated that glucuronidation and sulfation were the main metabolic pathways of Radix et Rhizoma Rhei and Radix Puerariae. In addition to glucuronidation and sulfation, other conjugation reactions also occurred in the metabolisms of Rhizoma Ligustici Chuanxiong such as cysteine conjugation and acetylcysteine conjugation, while phase I reactions (e.g., deglycosylated, hydroxylated) were the major metabolic reaction for Radix Ginseng. Many compounds from its single herb-dosed groups presented different absorption trends and slower elimination rates in the urine from the NMT-dosed group compared with the urine from the single-dosed groups. These results will provide helpful information for further basic research into the active substances in NaoMaiTong.

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Authors and Affiliations

  1. Guangdong Pharmaceutical University, Xiaoguwei Street, Panyu District, Guangzhou, 510006, China

    Xulei Fan, Yueying Rong & Shumei Wang

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  1. Xulei Fan
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  2. Yueying Rong
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  3. Shumei Wang
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Correspondence to Shumei Wang.

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All applicable international, national, and institutional guidelines for the care and use of animals were followed.

Funding

This study was funded by 81274060 and 81473413.

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Fan, X., Rong, Y. & Wang, S. Analysis of NaoMaiTong Metabolites Using High-Performance Liquid Chromatography/High-Resolution Mass Spectrometry in Rat Urine. Chromatographia 80, 1371–1399 (2017). https://doi.org/10.1007/s10337-017-3363-6

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