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Metabolism of Rhizoma coptidis in Human Urine by Ultra-High-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry

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European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Abstract

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.

Methods

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.

Results

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.

Conclusions

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.

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Authors and Affiliations

  1. Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, 028000, People’s Republic of China

    Qingshan Zhang, Gaowa Wang, Risu Na, Haburi Jin, Ping Li & Renbatu Bu

  2. Department of Chinese Pharmacy, Beijing Friendship Hospital Affiliated to Capital University of Medical Sciences, Beijing, 100050, China

    Xi Chen

  3. Medical Institution Conducting Clinical Trials for Human Used Drug of Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, 028000, China

    Zhiqiang Han

  4. Mongolian Medicine College of Pharmacy of Inner Mongolia University for the Nationalities, Tongliao, 028000, China

    Xiangmei Chen

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  1. Qingshan Zhang
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  3. Xi Chen
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Correspondence to Renbatu Bu.

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Funding

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.

Ethical approval

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.

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Zhang, Q., Wang, G., Chen, X. et al. Metabolism of Rhizoma coptidis in Human Urine by Ultra-High-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry. Eur J Drug Metab Pharmacokinet 43, 441–452 (2018). https://doi.org/10.1007/s13318-018-0463-0

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  • DOI: https://doi.org/10.1007/s13318-018-0463-0

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