Metabolism of Rhizoma coptidis in Human Urine by Ultra-High-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry
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 m...
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| Veröffentlicht in: | European journal of drug metabolism and pharmacokinetics 2018-08, Vol.43 (4), p.441-452 |
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| creator | Zhang, Qingshan Wang, Gaowa Chen, Xi Han, Zhiqiang Chen, Xiangmei Na, Risu Jin, Haburi Li, Ping Bu, Renbatu |
| description | 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. |
| doi_str_mv | 10.1007/s13318-018-0463-0 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2003040426</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2003040426</sourcerecordid><originalsourceid>FETCH-LOGICAL-c344t-a7fe39fea2f78a8c5c8bfde875eb7b686bcde80dc296cb8c50f0fcd035c086ad3</originalsourceid><addsrcrecordid>eNp9Uc2O0zAQthCIrZZ9AC7IRy6BSZzYzhFVQJG6Ai30bDnOuPEqibO2o1V5Bh4aly4cGWk0Gn8_kucj5HUJ70oA8T6WjJWygHPXnBXwjGyqEsT5BZ6TDTAhC9FyfkVuYryHXEy2TcNfkquqrRsQIDfk1y0m3fnRxYl6S-8G99NPmhq_JNe7SN1Md-ukZ3oIbkbanehhTEEXO3ccim8YrA8ZNUj37mF1Pd0OIeuTPwa9DCe69esyYk8fXRroH80dRj-uyfmZ3uoY6fcFTcoaTOH0iryweox48zSvyeHTxx_bXbH_-vnL9sO-MKyuU6GFRdZa1JUVUkvTGNnZHqVosBMdl7wzeYPeVC03XcbBgjU9sMaA5Lpn1-TtxXcJ_mHFmNTkosFx1DP6NaoqnwpqqCueqeWFaoKPMaBVS3CTDidVgjrnoC45KDh3zkFB1rx5sl-7Cft_ir9Xz4TqQogZmo8Y1L1fw5y__B_X300clqU</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2003040426</pqid></control><display><type>article</type><title>Metabolism of Rhizoma coptidis in Human Urine by Ultra-High-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry</title><source>MEDLINE</source><source>SpringerLink (Online service)</source><creator>Zhang, Qingshan ; Wang, Gaowa ; Chen, Xi ; Han, Zhiqiang ; Chen, Xiangmei ; Na, Risu ; Jin, Haburi ; Li, Ping ; Bu, Renbatu</creator><creatorcontrib>Zhang, Qingshan ; Wang, Gaowa ; Chen, Xi ; Han, Zhiqiang ; Chen, Xiangmei ; Na, Risu ; Jin, Haburi ; Li, Ping ; Bu, Renbatu</creatorcontrib><description>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.</description><identifier>ISSN: 0378-7966</identifier><identifier>EISSN: 2107-0180</identifier><identifier>DOI: 10.1007/s13318-018-0463-0</identifier><identifier>PMID: 29450708</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Alkaloids - chemistry ; Alkaloids - urine ; Biomedical and Life Sciences ; Biomedicine ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal - pharmacokinetics ; Human Physiology ; Humans ; Mass Spectrometry ; Medical Biochemistry ; Molecular Structure ; Original Research Article ; Pharmaceutical Sciences/Technology ; Pharmacology/Toxicology ; Pharmacy</subject><ispartof>European journal of drug metabolism and pharmacokinetics, 2018-08, Vol.43 (4), p.441-452</ispartof><rights>Springer International Publishing AG, part of Springer Nature 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c344t-a7fe39fea2f78a8c5c8bfde875eb7b686bcde80dc296cb8c50f0fcd035c086ad3</citedby><cites>FETCH-LOGICAL-c344t-a7fe39fea2f78a8c5c8bfde875eb7b686bcde80dc296cb8c50f0fcd035c086ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13318-018-0463-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13318-018-0463-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29450708$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Qingshan</creatorcontrib><creatorcontrib>Wang, Gaowa</creatorcontrib><creatorcontrib>Chen, Xi</creatorcontrib><creatorcontrib>Han, Zhiqiang</creatorcontrib><creatorcontrib>Chen, Xiangmei</creatorcontrib><creatorcontrib>Na, Risu</creatorcontrib><creatorcontrib>Jin, Haburi</creatorcontrib><creatorcontrib>Li, Ping</creatorcontrib><creatorcontrib>Bu, Renbatu</creatorcontrib><title>Metabolism of Rhizoma coptidis in Human Urine by Ultra-High-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry</title><title>European journal of drug metabolism and pharmacokinetics</title><addtitle>Eur J Drug Metab Pharmacokinet</addtitle><addtitle>Eur J Drug Metab Pharmacokinet</addtitle><description>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.</description><subject>Alkaloids - chemistry</subject><subject>Alkaloids - urine</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Drugs, Chinese Herbal - pharmacokinetics</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Mass Spectrometry</subject><subject>Medical Biochemistry</subject><subject>Molecular Structure</subject><subject>Original Research Article</subject><subject>Pharmaceutical Sciences/Technology</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><issn>0378-7966</issn><issn>2107-0180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uc2O0zAQthCIrZZ9AC7IRy6BSZzYzhFVQJG6Ai30bDnOuPEqibO2o1V5Bh4aly4cGWk0Gn8_kucj5HUJ70oA8T6WjJWygHPXnBXwjGyqEsT5BZ6TDTAhC9FyfkVuYryHXEy2TcNfkquqrRsQIDfk1y0m3fnRxYl6S-8G99NPmhq_JNe7SN1Md-ukZ3oIbkbanehhTEEXO3ccim8YrA8ZNUj37mF1Pd0OIeuTPwa9DCe69esyYk8fXRroH80dRj-uyfmZ3uoY6fcFTcoaTOH0iryweox48zSvyeHTxx_bXbH_-vnL9sO-MKyuU6GFRdZa1JUVUkvTGNnZHqVosBMdl7wzeYPeVC03XcbBgjU9sMaA5Lpn1-TtxXcJ_mHFmNTkosFx1DP6NaoqnwpqqCueqeWFaoKPMaBVS3CTDidVgjrnoC45KDh3zkFB1rx5sl-7Cft_ir9Xz4TqQogZmo8Y1L1fw5y__B_X300clqU</recordid><startdate>20180801</startdate><enddate>20180801</enddate><creator>Zhang, Qingshan</creator><creator>Wang, Gaowa</creator><creator>Chen, Xi</creator><creator>Han, Zhiqiang</creator><creator>Chen, Xiangmei</creator><creator>Na, Risu</creator><creator>Jin, Haburi</creator><creator>Li, Ping</creator><creator>Bu, Renbatu</creator><general>Springer International Publishing</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20180801</creationdate><title>Metabolism of Rhizoma coptidis in Human Urine by Ultra-High-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry</title><author>Zhang, Qingshan ; Wang, Gaowa ; Chen, Xi ; Han, Zhiqiang ; Chen, Xiangmei ; Na, Risu ; Jin, Haburi ; Li, Ping ; Bu, Renbatu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c344t-a7fe39fea2f78a8c5c8bfde875eb7b686bcde80dc296cb8c50f0fcd035c086ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Alkaloids - chemistry</topic><topic>Alkaloids - urine</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Drugs, Chinese Herbal - pharmacokinetics</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Mass Spectrometry</topic><topic>Medical Biochemistry</topic><topic>Molecular Structure</topic><topic>Original Research Article</topic><topic>Pharmaceutical Sciences/Technology</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Qingshan</creatorcontrib><creatorcontrib>Wang, Gaowa</creatorcontrib><creatorcontrib>Chen, Xi</creatorcontrib><creatorcontrib>Han, Zhiqiang</creatorcontrib><creatorcontrib>Chen, Xiangmei</creatorcontrib><creatorcontrib>Na, Risu</creatorcontrib><creatorcontrib>Jin, Haburi</creatorcontrib><creatorcontrib>Li, Ping</creatorcontrib><creatorcontrib>Bu, Renbatu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of drug metabolism and pharmacokinetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Qingshan</au><au>Wang, Gaowa</au><au>Chen, Xi</au><au>Han, Zhiqiang</au><au>Chen, Xiangmei</au><au>Na, Risu</au><au>Jin, Haburi</au><au>Li, Ping</au><au>Bu, Renbatu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolism of Rhizoma coptidis in Human Urine by Ultra-High-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry</atitle><jtitle>European journal of drug metabolism and pharmacokinetics</jtitle><stitle>Eur J Drug Metab Pharmacokinet</stitle><addtitle>Eur J Drug Metab Pharmacokinet</addtitle><date>2018-08-01</date><risdate>2018</risdate><volume>43</volume><issue>4</issue><spage>441</spage><epage>452</epage><pages>441-452</pages><issn>0378-7966</issn><eissn>2107-0180</eissn><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.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>29450708</pmid><doi>10.1007/s13318-018-0463-0</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0378-7966 |
| ispartof | European journal of drug metabolism and pharmacokinetics, 2018-08, Vol.43 (4), p.441-452 |
| issn | 0378-7966 2107-0180 |
| language | eng |
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| source | MEDLINE; SpringerLink (Online service) |
| subjects | Alkaloids - chemistry Alkaloids - urine Biomedical and Life Sciences Biomedicine Chromatography, High Pressure Liquid Drugs, Chinese Herbal - pharmacokinetics Human Physiology Humans Mass Spectrometry Medical Biochemistry Molecular Structure Original Research Article Pharmaceutical Sciences/Technology Pharmacology/Toxicology Pharmacy |
| title | Metabolism of Rhizoma coptidis in Human Urine by Ultra-High-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry |
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