Metabolism of Rhizoma coptidis in Human Urine by Ultra-High-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry
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Background and Objectives
Rhizoma coptidis extract and its alkaloids were reported to exhibit various pharmacological activities. However, pharmacokinetics investigations indicated that the plasma concentrations of the alkaloids were too low to explain their systemic therapeutic actions. Thus, the metabolic profile of Rhizoma coptidis in humans is yet to be fully investigated and the present study aimed to investigate the metabolic profile of Rhizoma coptidis in human urine after oral administration of Rhizoma coptidis extract.
In this study, the metabolism of Rhizoma coptidis at a clinical dose (5 g/60 kg/day) was investigated using ultra-high-performance liquid chromatography coupled with high-resolution LTQ-Orbitrap mass spectrometry.
Totally, 30 constituents including 7 prototypes, 5 sulfation metabolites and 18 glucuronide conjugates were elucidated and identified on the basis of the characteristics of their high-resolution precursor ions, product ions, and chromatographic retention times in human urine. Among the 7 prototypes, 3 prototypes (M20, M26 and M28) were identified definitely by comparing with standards. Based on the metabolites detected in human urine, a possible metabolic pathway of Rhizoma coptidis in vivo was proposed.
The results demonstrated that the metabolic fate of Rhizoma coptidis mainly involved sulfation and glucuronidation in human urine and the glucuronide conjugate M14 (berberrubinen-9-O-glucuronide) might be a pharmacokinetic marker for Rhizoma coptidis alkaloids in humans. This study will be helpful to comprehensively understand the metabolic process of Rhizoma coptidis and how Rhizoma coptidis shows its pharmacological effects in humans.
Compliance with Ethical Standards
The work was supported by the innovation team of the education department of the Inner Mongolia autonomous region (No. NMGIRT-A1606).
Conflict of interest
Qingshan Zhang, Gaowa Wang, Xi Chen, Zhiqiang Han, Xiangmei Chen, Risu Na, Haburi Jin, Ping Li and Renbatu Bu have declared no conflict of interest.
This study was ethically approved by the Medical Ethics Committee of Affiliated Hospital of Inner Mongolia University for the Nationalities (Tongliao, China). Informed consent was obtained from all individual participants included in the study. All procedures performed in this study involving human participants were in accordance with the ethical standards of the Medical Ethics Committee of Affiliated Hospital of Inner Mongolia University for the Nationalities and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
- 1.Ho CE, Goh YL, Zhang C. From prejudice to evidence: the case of Rhizoma coptidis in Singapore. Evid Based Complement Altern Med. 2014;2014:871720.Google Scholar
- 10.Pang B, Yu XT, Zhou Q, Zhao TY, Wang H, Gu CJ, et al. Effect of Rhizoma coptidis (Huang Lian) on treating diabetes mellitus. Evid Based Complement Altern Med. 2015;2015:921416.Google Scholar
- 23.Qian XC, Zhang L, Tao Y, Huang P, Li JS, Chai C, et al. Simultaneous determination of ten alkaloids of crude and wine-processed Rhizoma Coptidis aqueous extracts in rat plasma by UHPLC–ESI-MS/MS and its application to a comparative pharmacokinetic study. J Pharm Biomed Anal. 2015;105:64–73.CrossRefPubMedGoogle Scholar
- 29.Ren W, Xin SK, Han LY, Zuo R, Li Y, Gong MX, et al. Comparative metabolism of four limonoids in human liver microsomes using ultra-high-performance liquid chromatography coupled with high-resolution LTQ-Orbitrap mass spectrometry. Rapid Commun Mass Spectrom. 2015;29(21):2045–56.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Zhang XS, Ren W, Bian BL, Zhao HY, Wang S. Comparative metabolism of tussilagone in rat and human liver microsomes using ultra-high-performance liquid chromatography coupled with high-resolution LTQ-Orbitrap mass spectrometry. Rapid Commun Mass Spectrom. 2015;29(18):1641–50.CrossRefPubMedGoogle Scholar
- 31.Ren W, Li Y, Zuo R, Wang HJ, Si N, Zhao HY, et al. Species-related difference between limonin and obacunone among five liver microsomes and zebrafish using ultra-high-performance liquid chromatography coupled with a LTQ-Orbitrap mass spectrometer. Rapid Commun Mass Spectrom. 2014;28(21):2292–300.CrossRefPubMedGoogle Scholar
- 38.Zhang QS, Wang GW, Han ZQ, Chen XM, Na R, Jin H, et al. Metabolic profile of Rhizoma coptidis in human plasma determined using ultra high-performance liquid chromatography coupled with high-resolution mass spectrometry. Rapid Commun Mass Spectrom. 2017. https://doi.org/10.1002/rcm.7990.CrossRefPubMedPubMedCentralGoogle Scholar
- 39.Zuo R, Ren W, Bian BL, Wang HJ, Wang YN, Hu H, et al. Metabolic fate analysis of Huang-Lian-Jie-Du Decoction in rat urine and feces by LC–IT-MS combining with LC–FT-ICR-MS: a feasible strategy for the metabolism study of Chinese medical formula. Xenobiotica. 2016;46(1):65–81.CrossRefPubMedGoogle Scholar