Characterization and identification of the metabolites of dihydromethysticin by ultra‐high‐performance liquid chromatography orbitrap high‐resolution mass spectrometry
Dihydromethysticin, a natural component from Piper methysticum Forst, has been reported to display pharmacological effects in mental disorders and some malignant tumors. However, the metabolism of this component remained unknown. The goal of this work was conducted to discover the metabolic profiles...
Saved in:
| Published in | Journal of separation science Vol. 45; no. 15; pp. 2914 - 2923 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Germany
Wiley Subscription Services, Inc
01.08.2022
|
| Subjects | |
| Online Access | Get full text |
| ISSN | 1615-9306 1615-9314 1615-9314 |
| DOI | 10.1002/jssc.202200250 |
Cover
| Abstract | Dihydromethysticin, a natural component from Piper methysticum Forst, has been reported to display pharmacological effects in mental disorders and some malignant tumors. However, the metabolism of this component remained unknown. The goal of this work was conducted to discover the metabolic profiles of dihydromethysticin. The in vitro incubation was performed by incubating dihydromethysticin with rat, monkey, and human liver microsomes and hepatocytes. An analytical assay of ultra‐high performance liquid chromatography combined with Orbitrap high‐resolution mass spectrometry was utilized to detect and identify the metabolites. With high resolution mass spectrometric determination, the accurate mass, elemental composition, and product ions of the metabolites were determined, which enabled structural characterization to become easy. Under the present conditions, four phase‐I metabolites, as well as six phase‐II metabolites, were detected and their tentative structures were characterized by mass spectra. M4 was found as the most abundant metabolite both in liver microsomes and hepatocytes. Cytochrome P450 1A2, 2C9, and 3A4 contributed to the formation of this metabolite by using human recombinant P450 enzymes. M4 can be oxidized into reactive ortho‐quinone intermediate followed by conjugating with glutathione. M4 was also subject to glucuronidation (M1 and M2) and methylation (M5). Demethylenation, oxidation, hydroxylation, glucuronidation, glutathionylation, and methylation were the primary metabolic pathways of dihydromethysticin. This study provides in vitro metabolism data of dihydromethysticin, which is indispensable for understanding the disposition of this compound. |
|---|---|
| AbstractList | Dihydromethysticin, a natural component from Piper methysticum Forst, has been reported to display pharmacological effects in mental disorders and some malignant tumors. However, the metabolism of this component remained unknown. The goal of this work was conducted to discover the metabolic profiles of dihydromethysticin. The in vitro incubation was performed by incubating dihydromethysticin with rat, monkey, and human liver microsomes and hepatocytes. An analytical assay of ultra‐high performance liquid chromatography combined with Orbitrap high‐resolution mass spectrometry was utilized to detect and identify the metabolites. With high resolution mass spectrometric determination, the accurate mass, elemental composition, and product ions of the metabolites were determined, which enabled structural characterization to become easy. Under the present conditions, four phase‐I metabolites, as well as six phase‐II metabolites, were detected and their tentative structures were characterized by mass spectra. M4 was found as the most abundant metabolite both in liver microsomes and hepatocytes. Cytochrome P450 1A2, 2C9, and 3A4 contributed to the formation of this metabolite by using human recombinant P450 enzymes. M4 can be oxidized into reactive ortho‐quinone intermediate followed by conjugating with glutathione. M4 was also subject to glucuronidation (M1 and M2) and methylation (M5). Demethylenation, oxidation, hydroxylation, glucuronidation, glutathionylation, and methylation were the primary metabolic pathways of dihydromethysticin. This study provides in vitro metabolism data of dihydromethysticin, which is indispensable for understanding the disposition of this compound. Dihydromethysticin, a natural component from Piper methysticum Forst, has been reported to display pharmacological effects in mental disorders and some malignant tumors. However, the metabolism of this component remained unknown. The goal of this work was conducted to discover the metabolic profiles of dihydromethysticin. The in vitro incubation was performed by incubating dihydromethysticin with rat, monkey and human liver microsomes and hepatocytes. An analytical assay of ultra-high performance liquid chromatography combined with Orbitrap high resolution mass spectrometry was utilized to detect and identify the metabolites. With high resolution mass spectrometric determination, the accurate mass, elemental composition and product ions of the metabolites were determined, which enabled structural characterization becoming easy. Under the present conditions, four phase I metabolites as well as six phase II metabolites were detected and their tentative structures were characterized by mass spectra. M4 was found as the most abundant metabolite both in liver microsomes and hepatocytes. Cytochrome P450 1A2, 2C9 and 3A4 contributed to the formation of this metabolite by using human recombinant P450 enzymes. M4 can be oxidized into reactive ortho-quinone intermediate followed by conjugating with glutathione. M4 was also subject to glucuronidation (M1 and M2) and methylation (M5). Demethylenation, oxidation, hydroxylation, glucuronidation, glutathionylation and methylation were the primary metabolic pathways of dihydromethysticin. This study provides in vitro metabolism data of dihydromethysticin, which is indispensable for understanding the disposition of this compound. This article is protected by copyright. All rights reserved. Dihydromethysticin, a natural component from Piper methysticum Forst, has been reported to display pharmacological effects in mental disorders and some malignant tumors. However, the metabolism of this component remained unknown. The goal of this work was conducted to discover the metabolic profiles of dihydromethysticin. The in vitro incubation was performed by incubating dihydromethysticin with rat, monkey, and human liver microsomes and hepatocytes. An analytical assay of ultra-high performance liquid chromatography combined with Orbitrap high-resolution mass spectrometry was utilized to detect and identify the metabolites. With high resolution mass spectrometric determination, the accurate mass, elemental composition, and product ions of the metabolites were determined, which enabled structural characterization to become easy. Under the present conditions, four phase-I metabolites, as well as six phase-II metabolites, were detected and their tentative structures were characterized by mass spectra. M4 was found as the most abundant metabolite both in liver microsomes and hepatocytes. Cytochrome P450 1A2, 2C9, and 3A4 contributed to the formation of this metabolite by using human recombinant P450 enzymes. M4 can be oxidized into reactive ortho-quinone intermediate followed by conjugating with glutathione. M4 was also subject to glucuronidation (M1 and M2) and methylation (M5). Demethylenation, oxidation, hydroxylation, glucuronidation, glutathionylation, and methylation were the primary metabolic pathways of dihydromethysticin. This study provides in vitro metabolism data of dihydromethysticin, which is indispensable for understanding the disposition of this compound.Dihydromethysticin, a natural component from Piper methysticum Forst, has been reported to display pharmacological effects in mental disorders and some malignant tumors. However, the metabolism of this component remained unknown. The goal of this work was conducted to discover the metabolic profiles of dihydromethysticin. The in vitro incubation was performed by incubating dihydromethysticin with rat, monkey, and human liver microsomes and hepatocytes. An analytical assay of ultra-high performance liquid chromatography combined with Orbitrap high-resolution mass spectrometry was utilized to detect and identify the metabolites. With high resolution mass spectrometric determination, the accurate mass, elemental composition, and product ions of the metabolites were determined, which enabled structural characterization to become easy. Under the present conditions, four phase-I metabolites, as well as six phase-II metabolites, were detected and their tentative structures were characterized by mass spectra. M4 was found as the most abundant metabolite both in liver microsomes and hepatocytes. Cytochrome P450 1A2, 2C9, and 3A4 contributed to the formation of this metabolite by using human recombinant P450 enzymes. M4 can be oxidized into reactive ortho-quinone intermediate followed by conjugating with glutathione. M4 was also subject to glucuronidation (M1 and M2) and methylation (M5). Demethylenation, oxidation, hydroxylation, glucuronidation, glutathionylation, and methylation were the primary metabolic pathways of dihydromethysticin. This study provides in vitro metabolism data of dihydromethysticin, which is indispensable for understanding the disposition of this compound. Dihydromethysticin, a natural component from Piper methysticum Forst, has been reported to display pharmacological effects in mental disorders and some malignant tumors. However, the metabolism of this component remained unknown. The goal of this work was conducted to discover the metabolic profiles of dihydromethysticin. The in vitro incubation was performed by incubating dihydromethysticin with rat, monkey, and human liver microsomes and hepatocytes. An analytical assay of ultra‐high performance liquid chromatography combined with Orbitrap high‐resolution mass spectrometry was utilized to detect and identify the metabolites. With high resolution mass spectrometric determination, the accurate mass, elemental composition, and product ions of the metabolites were determined, which enabled structural characterization to become easy. Under the present conditions, four phase‐I metabolites, as well as six phase‐II metabolites, were detected and their tentative structures were characterized by mass spectra. M4 was found as the most abundant metabolite both in liver microsomes and hepatocytes. Cytochrome P450 1A2, 2C9, and 3A4 contributed to the formation of this metabolite by using human recombinant P450 enzymes. M4 can be oxidized into reactive ortho ‐quinone intermediate followed by conjugating with glutathione. M4 was also subject to glucuronidation (M1 and M2) and methylation (M5). Demethylenation, oxidation, hydroxylation, glucuronidation, glutathionylation, and methylation were the primary metabolic pathways of dihydromethysticin. This study provides in vitro metabolism data of dihydromethysticin, which is indispensable for understanding the disposition of this compound. |
| Author | Cheng, Cong Zhao, Shanshan Pang, Jie Gu, Yong‐Li Zhao, Yanyun |
| Author_xml | – sequence: 1 givenname: Cong surname: Cheng fullname: Cheng, Cong organization: The First Affiliated Hospital of Kangda College of Nanjing Medical University/The First People's Hospital of Lianyungang – sequence: 2 givenname: Shanshan surname: Zhao fullname: Zhao, Shanshan organization: Jiangsu Wanbang Pharmaceutical Technology Co. Ltd – sequence: 3 givenname: Yong‐Li surname: Gu fullname: Gu, Yong‐Li organization: The First Affiliated Hospital of Kangda College of Nanjing Medical University/The First People's Hospital of Lianyungang – sequence: 4 givenname: Jie surname: Pang fullname: Pang, Jie organization: The First Affiliated Hospital of Kangda College of Nanjing Medical University/The First People's Hospital of Lianyungang – sequence: 5 givenname: Yanyun orcidid: 0000-0002-3998-6124 surname: Zhao fullname: Zhao, Yanyun email: zyy13327865383@163.com organization: Lianyungang Hospital of Traditional Chinese Medicine |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35689602$$D View this record in MEDLINE/PubMed |
| BookMark | eNqFkstu1TAQhi1URC-wZYkssWFzTn2LEy_REVdV6qKwtnxL46MkTm1HKKx4BF6El-JJ8Lm0i0qoqxmPvn9-jWfOwckYRgfAa4zWGCFyuU3JrAkipDwq9AycYY6rlaCYnTzkiJ-C85S2COG6EegFOKUVbwRH5Az82XQqKpNd9D9V9mGEarTQWzdm33pzKIUW5s7BwWWlQ--zS7uS9d1iYyjVbknZGz9CvcC5z1H9_fW787ddCZOLbYiDGo2Dvb-bvYWmKyKVw21UU7fAELUvkgkeFdGl0M9730GlBNPkTN7bxOUleN6qPrlXx3gBvn_88G3zeXV1_enL5v3VylCKxYoxw4TSDbPWYstww4zmVAnGDUZY00bUDPNd5hRTTpOKOFtppItEVYrQC_Du0HeK4W52KcvBJ-P6Xo0uzEmSGjeUI9aIp1FeV8WK1lVB3z5Ct2GOYxmkNESENlw0rFBvjtSsB2flFP2g4iLvd1YAdgBMDClF10rj835R5Rt9LzGSu9OQu9OQD6dRZOtHsvvO_xUcfX743i1P0PLrzc2mrrGg_wD4h9Lw |
| CitedBy_id | crossref_primary_10_1007_s43188_023_00211_2 crossref_primary_10_1002_jssc_202200617 crossref_primary_10_1002_jssc_202200894 |
| Cites_doi | 10.1021/tx4001144 10.1016/S0031-9422(03)00381-9 10.1021/tx200168d 10.1111/j.1440-1681.1990.tb01349.x 10.1002/jssc.202000951 10.1021/acs.chemrestox.6b00203 10.1021/tx100412m 10.1016/S0006-2952(98)00268-8 10.1093/toxsci/kfh067 10.1002/rcm.8975 10.1055/s-2000-8625 10.1016/j.phymed.2016.11.002 10.1124/dmd.30.11.1153 10.1080/10590500801907407 10.1002/mc.23182 10.2165/00023210-200216110-00002 10.1097/00004714-200002000-00014 10.1002/rcm.8947 10.1002/ptr.840 10.1093/carcin/bgu149 10.1016/j.pharmthera.2004.10.013 10.1124/dmd.120.000325 10.1124/dmd.117.079780 10.1021/acs.chemrestox.0c00017 10.1002/jssc.202100807 10.1055/s-2002-34443 10.1016/j.jep.2019.01.032 10.1016/j.jpba.2021.114222 |
| ContentType | Journal Article |
| Copyright | 2022 Wiley‐VCH GmbH. This article is protected by copyright. All rights reserved. 2022 Wiley-VCH GmbH. |
| Copyright_xml | – notice: 2022 Wiley‐VCH GmbH. – notice: This article is protected by copyright. All rights reserved. – notice: 2022 Wiley-VCH GmbH. |
| DBID | AAYXX CITATION NPM 7U5 8FD L7M 7X8 7S9 L.6 |
| DOI | 10.1002/jssc.202200250 |
| DatabaseName | CrossRef PubMed Solid State and Superconductivity Abstracts Technology Research Database Advanced Technologies Database with Aerospace MEDLINE - Academic AGRICOLA AGRICOLA - Academic |
| DatabaseTitle | CrossRef PubMed Technology Research Database Advanced Technologies Database with Aerospace Solid State and Superconductivity Abstracts MEDLINE - Academic AGRICOLA AGRICOLA - Academic |
| DatabaseTitleList | AGRICOLA Technology Research Database PubMed MEDLINE - Academic CrossRef |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Engineering Chemistry |
| EISSN | 1615-9314 |
| EndPage | 2923 |
| ExternalDocumentID | 35689602 10_1002_jssc_202200250 JSSC7719 |
| Genre | article Journal Article |
| GroupedDBID | --- .3N .GA .Y3 05W 0R~ 10A 1L6 1OC 31~ 33P 3SF 3WU 4.4 4ZD 50Y 50Z 51W 51X 52M 52N 52O 52P 52S 52T 52U 52W 52X 53G 5GY 5VS 66C 702 7PT 8-0 8-1 8-3 8-4 8-5 8UM 930 A03 AAESR AAEVG AAHBH AAHHS AAHQN AAMNL AANHP AANLZ AAONW AASGY AAXRX AAYCA AAZKR ABCUV ABDBF ABIJN ABJNI ABPVW ACAHQ ACBWZ ACCFJ ACCZN ACGFS ACIWK ACPOU ACRPL ACUHS ACXBN ACXQS ACYXJ ADBBV ADEOM ADIZJ ADKYN ADMGS ADNMO ADOZA ADXAS ADZMN AEEZP AEIGN AEIMD AENEX AEQDE AEUQT AEUYR AFBPY AFFPM AFGKR AFPWT AFWVQ AFZJQ AHBTC AI. AITYG AIURR AIWBW AJBDE AJXKR ALAGY ALMA_UNASSIGNED_HOLDINGS ALUQN ALVPJ AMBMR AMYDB ATUGU AUFTA AZBYB AZFZN AZVAB BAFTC BDRZF BFHJK BHBCM BMNLL BMXJE BNHUX BROTX BRXPI BY8 CS3 D-E D-F DCZOG DPXWK DR2 DRFUL DRSTM DU5 EBD EJD F00 F01 F04 F5P FEDTE G-S G.N GNP GODZA H.T H.X HGLYW HHZ HVGLF HZ~ IX1 J0M JPC KQQ LATKE LAW LC2 LC3 LEEKS LH4 LITHE LOXES LP6 LP7 LUTES LW6 LYRES MEWTI MK4 MRFUL MRSTM MSFUL MSSTM MXFUL MXSTM N04 N05 N9A NF~ NNB O66 O9- OIG P2P P2W P2X P4D PQQKQ Q.N Q11 QB0 QRW R.K RNS ROL RWI RX1 RYL SUPJJ TUS UB1 UPT VH1 W8V W99 WBFHL WBKPD WIH WIK WJL WOHZO WXSBR WYISQ XG1 XPP XV2 YQT ~IA ~KM ~WT AAMMB AAYXX ADMLS AEFGJ AEYWJ AGHNM AGQPQ AGXDD AGYGG AIDQK AIDYY CITATION NPM 1OB 7U5 8FD L7M 7X8 7S9 L.6 |
| ID | FETCH-LOGICAL-c3319-44c49ab84ddd1d4184cb63a946c101b389741601b3ea4aeb252ed5b0bb84a5a23 |
| IEDL.DBID | DR2 |
| ISSN | 1615-9306 1615-9314 |
| IngestDate | Fri Sep 05 17:19:03 EDT 2025 Fri Sep 05 07:12:42 EDT 2025 Fri Sep 12 10:30:37 EDT 2025 Wed Feb 19 02:24:30 EST 2025 Thu Apr 24 23:08:31 EDT 2025 Wed Oct 01 02:09:16 EDT 2025 Wed Jan 22 16:24:47 EST 2025 |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 15 |
| Keywords | metabolic pathway metabolite characterization cytochrome P450 Dihydromethysticin |
| Language | English |
| License | This article is protected by copyright. All rights reserved. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c3319-44c49ab84ddd1d4184cb63a946c101b389741601b3ea4aeb252ed5b0bb84a5a23 |
| Notes | These authors contributed equally to this work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| ORCID | 0000-0002-3998-6124 |
| PMID | 35689602 |
| PQID | 2702386984 |
| PQPubID | 105495 |
| PageCount | 10 |
| ParticipantIDs | proquest_miscellaneous_2718360489 proquest_miscellaneous_2675601375 proquest_journals_2702386984 pubmed_primary_35689602 crossref_citationtrail_10_1002_jssc_202200250 crossref_primary_10_1002_jssc_202200250 wiley_primary_10_1002_jssc_202200250_JSSC7719 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | August 2022 |
| PublicationDateYYYYMMDD | 2022-08-01 |
| PublicationDate_xml | – month: 08 year: 2022 text: August 2022 |
| PublicationDecade | 2020 |
| PublicationPlace | Germany |
| PublicationPlace_xml | – name: Germany – name: Weinheim |
| PublicationTitle | Journal of separation science |
| PublicationTitleAlternate | J Sep Sci |
| PublicationYear | 2022 |
| Publisher | Wiley Subscription Services, Inc |
| Publisher_xml | – name: Wiley Subscription Services, Inc |
| References | 2002; 16 2021; 2003 2013; 26 2002; 30 1990; 17 2000; 66 2017; 24 2000; 20 2022; 45 2020; 59 2020; 34 2020; 33 2018; 46 2021; 35 2018; 9 2004; 79 2005; 106 2003; 68 1999; 57 2008; 26 2020; 49 2014; 35 2019; 235 2001; 15 2011; 24 2020; 43 2016; 29 2003; 64 e_1_2_7_6_1 e_1_2_7_5_1 e_1_2_7_4_1 e_1_2_7_3_1 e_1_2_7_9_1 e_1_2_7_8_1 e_1_2_7_7_1 e_1_2_7_19_1 e_1_2_7_18_1 e_1_2_7_17_1 e_1_2_7_2_1 e_1_2_7_15_1 e_1_2_7_14_1 e_1_2_7_13_1 e_1_2_7_12_1 e_1_2_7_11_1 e_1_2_7_10_1 e_1_2_7_26_1 e_1_2_7_27_1 e_1_2_7_28_1 e_1_2_7_29_1 e_1_2_7_30_1 e_1_2_7_25_1 e_1_2_7_24_1 e_1_2_7_23_1 e_1_2_7_22_1 Li ZQ (e_1_2_7_16_1) 2018; 9 e_1_2_7_21_1 e_1_2_7_20_1 |
| References_xml | – volume: 24 start-page: 992 year: 2011 end-page: 1002 article-title: Constituents in kava extracts potentially involved in hepatotoxicity: a review publication-title: Chem Res Toxicol. – volume: 24 start-page: 1 year: 2017 end-page: 13 article-title: Traditional preparations of kava (Piper methysticum) inhibit the growth of human colon cancer cells in vitro publication-title: Phytomedicine – volume: 26 start-page: 89 year: 2008 end-page: 112 article-title: Toxicity of kava publication-title: J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. – volume: 79 start-page: 106 year: 2004 end-page: 11 article-title: In vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactones publication-title: Toxicol Sci. – volume: 235 start-page: 301 year: 2019 end-page: 8 article-title: Chemical and in vitro toxicity analysis of a supercritical fluid extract of Kava (Piper methysticum) publication-title: J Ethnopharmacol. – volume: 59 start-page: 575 year: 2020 end-page: 89 article-title: Dihydromethysticin, a natural molecule from Kava, suppresses the growth of colorectal cancer via the NLRC3/PI3K pathway publication-title: Mol Carcinog – volume: 57 start-page: 465 year: 1999 end-page: 480 article-title: Integrated P450 reaction phenotyping: Attempting to bridge the gap between cDNA‐expressed cytochrome P450 and native human liver microsomes publication-title: Biochem. Pharmacol. – volume: 15 start-page: 549 year: 2001 end-page: 551 article-title: Kava and valerian in the treatment of stress‐induced insomnia publication-title: Phytother Res. – volume: 68 start-page: 784 year: 2003 end-page: 9 article-title: Kavain attenuates vascular contractility through inhibition of calcium channels publication-title: Planta Med – volume: 20 start-page: 84 issue: 1 year: 2000 end-page: 9 article-title: Efficacy of kava extract for treating anxiety: systematic review and meta‐analysis publication-title: J Clin Psychopharmacol. – volume: 34 year: 2020 article-title: Identification of the metabolites of piperine via hepatocyte incubation and liquid chromatography combined with diode‐array detection and high‐resolution mass spectrometry publication-title: Rapid Commun Mass Spectrom. – volume: 35 year: 2021 article-title: Identification of the stable and reactive metabolites of tetrahydropiperine using ultrahigh‐performance liquid chromatography combined with diode‐array detection and high‐resolution mass spectrometry publication-title: Rapid Commun Mass Spectrom. – volume: 45 start-page: 1222 year: 2022 end-page: 39 article-title: A comprehensive study of celastrol metabolism in vivo and in vitro using ultra‐high‐performance liquid chromatography coupled with hybrid triple quadrupole time‐of‐flight mass spectrometry publication-title: J Sep Sci. – volume: 29 start-page: 1828 year: 2016 end-page: 34 article-title: Dihydromethysticin (DHM) blocks tobacco carcinogen 4‐(methylnitrosamino)‐1‐ (3‐pyridyl)‐1‐butanone (NNK)‐induced O ‐methylguanine in a manner independent of the aryl hydrocarbon receptor (AhR) pathway in C57BL/6 female mice publication-title: Chem Res Toxicol. – volume: 49 start-page: 459 year: 2020 end-page: 69 article-title: Reversible and irreversible inhibition of cytochrome P450 enzymes by methylophiopogonanone a publication-title: Drug Metab Dispos. – volume: 16 start-page: 731 year: 2002 end-page: 43 article-title: Therapeutic potential of kava in the treatment of anxiety disorders publication-title: CNS Drugs – volume: 26 start-page: 926 year: 2013 end-page: 36 article-title: Bioactivation of sitaxentan in liver microsomes, hepatocytes, and expressed human P450s with characterization of the glutathione conjugate by liquid chromatography tandem mass spectrometry publication-title: Chem Res Toxicol. – volume: 2003 year: 2021 article-title: Characterization of the metabolites of irisflorentin by using ultra‐high performance liquid chromatography combined with quadrupole/orbitrap tandem mass spectrometry publication-title: J Pharm Biomed Anal. – volume: 30 start-page: 1153 year: 2002 end-page: 7 article-title: Inhibition of human cytochrome P450 activities by kava extract and kavalactones publication-title: Drug Metab. Dispos. – volume: 17 start-page: 495 year: 1990 end-page: 508 article-title: The antinociceptive actions of kava components in mice publication-title: Clin Exp Pharmacol Physiol. – volume: 35 start-page: 2365 year: 2014 end-page: 672 article-title: Dihydromethysticin from kava blocks tobacco carcinogen 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone‐ induced lung tumorigenesis and differentially reduces DNA damage in A/J mice publication-title: Carcinogenesis – volume: 24 start-page: 1345 year: 2011 end-page: 410 article-title: Structural alert/reactive metabolite concept as applied in medicinal chemistry to mitigate the risk of idiosyncratic drug toxicity: a perspective based on the critical examination of trends in the top 200 drugs marketed in the United States publication-title: Chem Res Toxicol. – volume: 9 year: 2018 article-title: The modulatory role of CYP3A4 in dictamnine‐induced hepatotoxicity publication-title: Front Pharmacol. – volume: 64 start-page: 673 year: 2003 end-page: 9 article-title: Kavalactones and the kava‐kava controversy publication-title: Phytochemistry – volume: 33 start-page: 1761 year: 2020 end-page: 9 article-title: Evidence for polyamine, biogenic amine, and amino acid adduction resulting from metabolic activation of diosbulbin B publication-title: Chem Res Toxicol. – volume: 66 start-page: 601 year: 2000 end-page: 606 article-title: Kavain inhibits murine airway smooth muscle contraction publication-title: Planta Med – volume: 43 start-page: 4405 year: 2020 end-page: 13 article-title: Metabolic profiling of ligustilide and identification of the metabolite in rat and human hepatocytes by liquid chromatography combined with high‐resolution mass spectrometry publication-title: J Sep Sci. – volume: 106 start-page: 97 year: 2005 end-page: 132 article-title: UDP‐glucuronosyltransferases and clinical drug‐drug interactions publication-title: Pharmacol Ther. – volume: 46 start-page: 1137 year: 2018 end-page: 45 article-title: Nitidine chloride is a mechanism‐based inactivator of CYP2D6 publication-title: Drug Metab Dispos – ident: e_1_2_7_30_1 doi: 10.1021/tx4001144 – ident: e_1_2_7_2_1 doi: 10.1016/S0031-9422(03)00381-9 – ident: e_1_2_7_21_1 doi: 10.1021/tx200168d – ident: e_1_2_7_5_1 doi: 10.1111/j.1440-1681.1990.tb01349.x – ident: e_1_2_7_23_1 doi: 10.1002/jssc.202000951 – ident: e_1_2_7_9_1 doi: 10.1021/acs.chemrestox.6b00203 – ident: e_1_2_7_14_1 doi: 10.1021/tx100412m – ident: e_1_2_7_25_1 doi: 10.1016/S0006-2952(98)00268-8 – ident: e_1_2_7_11_1 doi: 10.1093/toxsci/kfh067 – ident: e_1_2_7_20_1 doi: 10.1002/rcm.8975 – ident: e_1_2_7_6_1 doi: 10.1055/s-2000-8625 – ident: e_1_2_7_8_1 doi: 10.1016/j.phymed.2016.11.002 – ident: e_1_2_7_29_1 doi: 10.1124/dmd.30.11.1153 – ident: e_1_2_7_13_1 doi: 10.1080/10590500801907407 – ident: e_1_2_7_18_1 doi: 10.1002/mc.23182 – ident: e_1_2_7_17_1 doi: 10.2165/00023210-200216110-00002 – ident: e_1_2_7_4_1 doi: 10.1097/00004714-200002000-00014 – ident: e_1_2_7_19_1 doi: 10.1002/rcm.8947 – ident: e_1_2_7_7_1 doi: 10.1002/ptr.840 – ident: e_1_2_7_10_1 doi: 10.1093/carcin/bgu149 – ident: e_1_2_7_28_1 doi: 10.1016/j.pharmthera.2004.10.013 – ident: e_1_2_7_26_1 doi: 10.1124/dmd.120.000325 – ident: e_1_2_7_27_1 doi: 10.1124/dmd.117.079780 – ident: e_1_2_7_15_1 doi: 10.1021/acs.chemrestox.0c00017 – ident: e_1_2_7_22_1 doi: 10.1002/jssc.202100807 – ident: e_1_2_7_3_1 doi: 10.1055/s-2002-34443 – ident: e_1_2_7_12_1 doi: 10.1016/j.jep.2019.01.032 – volume: 9 year: 2018 ident: e_1_2_7_16_1 article-title: The modulatory role of CYP3A4 in dictamnine‐induced hepatotoxicity publication-title: Front Pharmacol. – ident: e_1_2_7_24_1 doi: 10.1016/j.jpba.2021.114222 |
| SSID | ssj0017890 |
| Score | 2.366669 |
| Snippet | Dihydromethysticin, a natural component from Piper methysticum Forst, has been reported to display pharmacological effects in mental disorders and some... Dihydromethysticin, a natural component from Piper methysticum Forst, has been reported to display pharmacological effects in mental disorders and some... |
| SourceID | proquest pubmed crossref wiley |
| SourceType | Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 2914 |
| SubjectTerms | Chromatography cytochrome P-450 cytochrome P450 Cytochromes P450 Dihydromethysticin elemental composition Glutathione hepatocytes High-performance liquid chromatography humans Hydroxylation Liver liver microsomes Mass spectra Mass spectrometry Mental disorders metabolic pathway Metabolism metabolite characterization Metabolites Methylation monkeys Oxidation Piper methysticum Quinones rats Scientific imaging separation Spectroscopy Structural analysis ultra-performance liquid chromatography |
| Title | Characterization and identification of the metabolites of dihydromethysticin by ultra‐high‐performance liquid chromatography orbitrap high‐resolution mass spectrometry |
| URI | https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fjssc.202200250 https://www.ncbi.nlm.nih.gov/pubmed/35689602 https://www.proquest.com/docview/2702386984 https://www.proquest.com/docview/2675601375 https://www.proquest.com/docview/2718360489 |
| Volume | 45 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVEBS databaseName: EBSCOhost Academic Search Ultimate customDbUrl: https://search.ebscohost.com/login.aspx?authtype=ip,shib&custid=s3936755&profile=ehost&defaultdb=asn eissn: 1615-9314 dateEnd: 20241003 omitProxy: true ssIdentifier: ssj0017890 issn: 1615-9306 databaseCode: ABDBF dateStart: 20121001 isFulltext: true titleUrlDefault: https://search.ebscohost.com/direct.asp?db=asn providerName: EBSCOhost – providerCode: PRVEBS databaseName: Inspec with Full Text customDbUrl: eissn: 1615-9314 dateEnd: 20241003 omitProxy: false ssIdentifier: ssj0017890 issn: 1615-9306 databaseCode: ADMLS dateStart: 20121001 isFulltext: true titleUrlDefault: https://www.ebsco.com/products/research-databases/inspec-full-text providerName: EBSCOhost – providerCode: PRVWIB databaseName: Wiley Online Library - Core collection (SURFmarket) issn: 1615-9306 databaseCode: DR2 dateStart: 20010101 customDbUrl: isFulltext: true eissn: 1615-9314 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0017890 providerName: Wiley-Blackwell |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3LThsxFLUQm9JFH_SVFipXqtTVQMb2PLxEEQghlQUUid3IHjti2jBJ57FIV_0EfoSf6pdwrz0zkFYFVd0kkXOd8ei-zs34HhPycRpCjrbxOEhFZAJhGA-UkqAQxUUyNlIKR7Hx-Tg-PBNH59H5nS5-zw8x_OGGnuHiNTq40vXuLWno17pGCkLGXBqHIBzyyD2nPRn4o0Ls8sSKC9J2IAEc96yNY7a7On01K_0BNVeRq0s9B0-J6hftd5x822kbvZP_-I3P8X_u6hl50uFSuucN6TlZs-UmeTTpj4PbJI_vMBe-INeTgejZ93FSVRpamG7vkR-aTynAS3ppG7A07HWuccgUF0tHkoAmgnu6S6qXtJ01lfr18wrpk-FtcdvPQGfF97YwNL-ASarpKLbpvNIFTFnQbkZley-il1AQUNdC6i5TLV-Ss4P9L5PDoDv5Icg5dlUJkQupdCqMMaERUIXmOuZKijiHEKIBZCGQxE9WCWU1i5g1kR5rmKIixfgrsl7OS_uGUJ0k0zzh8GrhV6Y8NQgrdZIiJS_UiiMS9JrP8o4WHU_nmGWe0JllqJJsUMmIfBrkF54Q5K-SW70hZV1gqDNs_-NpLFO48Ifha1AlPqdRpZ23IANFXIxUkNE9MoApeAzhV47Ia2-kw3LAD1IoTBncmjO1B9aZHZ2eTpIklG__Uf4d2cBBvx1yi6w3VWu3AaI1-r1zwxvu3Ttu |
| linkProvider | Wiley-Blackwell |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3NbtNAEB5BORQO_JS_QIFFQuLkNvGuf_aIAlUobQ-0lbhZu96Nakid4NiHcOIReBFeiidhZtd2CQgQ4pJEzqy91szsfGPPfAvwbDrCGG3jYZCKyATChDxQSqJCFBfJ0EgpHMXG4VE8ORX776KumpB6YTw_RP_AjTzDrdfk4PRAeveCNfT9ckkchGHo4vhluEIv6cg3X77tGaRG1OdJORcG7kAiPO54G4fh7vr49bj0C9hcx64u-OzdAN1N29ecfNhpar2Tf_qJ0fG_7usmXG-hKXvhbekWXLLlFmyOux3htuDaD-SFt-HruOd69q2cTJWGFaYtP_KH5lOGCJOd2xqNjdqdl3TIFGcrx5NAVkJl3SXTK9bM6kp9-_yFGJTxa3HR0sBmxcemMCw_w0Gqblm22bzSBQ5ZsHZEZTtHYueYEzDXReouU63uwOneq5PxJGg3fwhyTo1VQuRCKp0KY8zICExEcx1zJUWc4yqiEWcRlqRfVglldRiF1kR6qHGIilTI78JGOS_tfWA6SaZ5wvHT4lmmPDWELHWSEisvposDCDrVZ3nLjE4bdMwyz-kcZqSSrFfJAJ738gvPCfJbye3OkrJ2bVhm1AHI01imeOGn_d-oSnpVo0o7b1AG87iY2CCjP8ggrOAxrsByAPe8lfbT4VGcYm4a4q05W_vLPLP94-Nxkozkg3-UfwKbk5PDg-zg9dGbh3CVBHx15DZs1FVjHyFiq_Vj55PfAXEnP4o |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3NbtQwELagSPwcCpS_hQJGQuKUdjd2nPiIFlalQIUolXqL7NhRA9vskk0Oy6mP0BfhpfokzNhJ2gUBQlySKJlJHM3Y803i-UzI83wEMdqKYZDwyATchCxQSoJBFOPx0EjJHcXG-z2xc8B3D6PDC1X8nh-i_-CGPcON19jB5ybfPicN_bxYIAVhGLowfplc4QJSLIRFH3sCqRGWeWLKBXE7kICOO9rGYbi9qr8aln7BmqvQ1cWeyU2iulb7KSdftppab2XffiJ0_J_XukXWW2BKX3pPuk0u2XKDXBt368FtkBsXqAvvkO_jnunZF3JSVRpamHbykT81yyngS3psa3A1LHZe4ClTHC0dSwL6CE7qLqle0mZaV-rs5BT5k2E3Py9ooNPia1MYmh2Bkqpbjm06q3QBKnPaalS260b0GDIC6mpI3WOq5V1yMHn9abwTtEs_BBnDsirOMy6VTrgxZmQ4pKGZFkxJLjIYQzSgLESSeGQVV1aHUWhNpIcaVFSkQnaPrJWz0j4gVMdxnsUMthbukrPEIK7UcYKcvJAsDkjQWT7NWl50XJ5jmnpG5zBFk6S9SQbkRS8_94wgv5Xc7BwpbUeGRYr1fywRMoEHP-svgynxR40q7awBGcjiBHJBRn-QAVDBBIy_ckDueyftm8MikUBmGsKrOVf7SzvT3f39cRyP5MN_lH9Krn54NUnfvdl7-4hcx-t-auQmWaurxj4GuFbrJ65H_gCQ-j45 |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Characterization+and+identification+of+the+metabolites+of+dihydromethysticin+by+ultra%E2%80%90high%E2%80%90performance+liquid+chromatography+orbitrap+high%E2%80%90resolution+mass+spectrometry&rft.jtitle=Journal+of+separation+science&rft.au=Cheng%2C+Cong&rft.au=Zhao%2C+Shanshan&rft.au=Yong%E2%80%90Li+Gu&rft.au=Pang%2C+Jie&rft.date=2022-08-01&rft.pub=Wiley+Subscription+Services%2C+Inc&rft.issn=1615-9306&rft.eissn=1615-9314&rft.volume=45&rft.issue=15&rft.spage=2914&rft.epage=2923&rft_id=info:doi/10.1002%2Fjssc.202200250&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1615-9306&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1615-9306&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1615-9306&client=summon |