Article(id=1218263516671295821, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1218263514121163166, articleNumber=null, orderNo=null, doi=10.16438/j.0513-4870.2017-0670, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1499529600000, receivedDateStr=2017-07-09, revisedDate=1502121600000, revisedDateStr=2017-08-08, acceptedDate=null, acceptedDateStr=null, onlineDate=1768386256615, onlineDateStr=2026-01-14, pubDate=1510416000000, pubDateStr=2017-11-12, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1768386256615, onlineIssueDateStr=2026-01-14, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1768386256615, creator=13701087609, updateTime=1768386256615, updator=13701087609, issue=Issue{id=1218263514121163166, tenantId=1146029695717560320, journalId=1189982191388893191, year='2017', volume='52', issue='11', pageStart='1639', pageEnd='1776', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1768386256008, creator=13701087609, updateTime=1768386717926, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1218265451596010257, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1218263514121163166, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1218265451596010258, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1218263514121163166, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1743, endPage=1747, ext={EN=ArticleExt(id=1218263518244159829, articleId=1218263516671295821, tenantId=1146029695717560320, journalId=1189982191388893191, language=EN, title=Analysis of metabolites and metabolic pathway of 5F-AMB
in vitro using UPLC-HR-MS, columnId=1190335348761793317, journalTitle=Acta Pharmaceutica Sinica, columnName=ORIGINAL ARTICLES, runingTitle=null, highlight=null, articleAbstract=
This study was designed to investigate the metabolites of 5F-AMB by human liver microsomes model in vitro. 5F-AMB was added in the reaction mixture to simulate the metabolic process in human hepatocytes in vivo, and then to determine the reaction points and pathways of metabolism by ultra performance liquid chromatography (UPLC) coupled to high resolution mass spectrum (HR-MS). 5F-AMB generated 9 metabolites in total in the human liver microsomes model. Ester hydrolysis, combination of ester hydrolysis and oxidative defluorination, combination of ester hydrolysis and hydroxylation on pentyl chain moiety and combination of ester hydrolysis and hydroxylation on indazole ring moiety reactions were its main metabolic pathways. The method is fast and efficient so that the ester hydrolysis, combination of ester hydrolysis and oxidative defluorination, combination of ester hydrolysis and hydroxylation on pentyl chain moiety and combination of ester hydrolysis and hydroxylation on indazole ring moiety metabolites of 5F-AMB can be used as the suitable and potential biomarkers in the urine samples.
, correspAuthors=Jing LI, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright ©2017 Acta Pharmaceutica Sinica. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Jing LI, Zhen-dong HUA, You-mei WANG), CN=ArticleExt(id=1218263519288541577, articleId=1218263516671295821, tenantId=1146029695717560320, journalId=1189982191388893191, language=CN, title=超高效液相色谱-高分辨质谱联用分析新型毒品5F-AMB的体外肝微粒体代谢物及代谢途径, columnId=1190335348896011050, journalTitle=药学学报, columnName=研究论文, runingTitle=null, highlight=null, articleAbstract=
本文研究新型毒品5F-AMB在体外肝微粒体模型中的代谢物。在体外人肝微粒体孵育模型中加入5F-AMB以模拟在人体的代谢过程,并利用超高效液相色谱高分辨质谱联用技术(UPLC-HR-MS)分析代谢发生位点及代谢途径。结果显示,5F-AMB在人肝微粒体模型中共产生9种代谢物,其主要代谢途径为酯键水解、酯键水解合并脱氟氧化、酯键水解合并戊烷基链羟化和酯键水解合并吲唑环羟化。以上结果表明该方法简便快捷,推荐5F-AMB的酯键水解、酯键水解合并脱氟氧化、酯键水解合并戊烷基链羟化和酯键水解合并吲唑环羟化代谢物为合适的潜在尿液标志物。
, correspAuthors=李静, authorNote=null, correspAuthorsNote=
, copyrightStatement=版权所有©《药学学报》编辑部2017, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=W08DJWlb3TBY8AmojGKQkw==, magXml=UoHqUKynYv0wDOzkLRL2zQ==, pdfUrl=null, pdf=JV1QAwO9+51fr/+WiWX8XQ==, pdfFileSize=394778, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=C7ctEhXDQbm9t+6J+5GH3A==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=3Upzvu+HrRJMgQ2bx95hGw==, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=李静, 花镇东, 王优美)}, authors=[Author(id=1218968413070873452, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1218263516671295821, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=caroline1990717@sina.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1218968413163148153, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1218263516671295821, authorId=1218968413070873452, language=EN, stringName=Jing LI, firstName=Jing, middleName=null, lastName=LI, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=
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Chemical structure of 5F-AMB
, figureFileSmall=KtE9CIpoXR0qGOV5WdO05g==, figureFileBig=xnnPAF/v9LW3DbrkGVKc9w==, tableContent=null), ArticleFig(id=1218968417684607183, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1218263516671295821, language=EN, label=null, caption=null, figureFileSmall=gj3qBo4OgGNKP2j0oDMb5Q==, figureFileBig=UZM+olZOSfv+o4CPmEX90Q==, tableContent=null), ArticleFig(id=1218968417902711009, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1218263516671295821, language=CN, label=Figure 2, caption=
Combined extracted ion chromatograms of 5F-AMB and metabolites (M1-M9) identified in human liver microsomes
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Product ion mass spectra and assigned fragmentation patterns for 5F-AMB (a) and all metabolites (b-j) that were identified after human liver microsomes incubation. Markush bond indicates unassigned metabolic position
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Proposed metabolic pathways of 5F-AMB in human liver microsomes. Unassigned metabolic positions are depicted as Markush structures
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| Peak ID | Metabolic reaction | RT /min | Exact mass [M+H]+(m/z) | Accurate mass [M+H]+(m/z) | Mass error /ppm | Chemical formula | Fragment ion | Area | Rank |
| 5F-AMB | NA | 8.24 | 364.203 1 | 364.202 5 | -1.7 | C19H26FN3O3 | 251, 304, 233, 213, 145, 177, 163 | 9.9×106 | |
| M1 | Hydroxylation (pentyl) | 5.84 | 380.198 0 | 380.197 9 | -0.4 | C19H26FN3O4 | 251, 362, 145, 213, 330, 163 | 8.5×105 | 9 |
| M2 | Ester hydrolysis + hydroxylation (pentyl) | 3.49 | 366.182 4 | 366.181 7 | -1.9 | C18H24FN3O4 | 267, 145, 320 | 5.7×107 | 3 |
| M3 | Ester hydrolysis + hydroxylation (butane moiety) | 3.90 | 366.182 4 | 366.181 9 | -1.3 | C18H24FN3O4 | 251, 145, 233, 348 | 7.9×106 | 7 |
| M4 | | 4.25 | 366.182 4 | 366.181 9 | -1.3 | C18H24FN3O4 | 251, 348, 145, 233, 213, 330, 177 | 1.2×107 | 5 |
| M5 | Ester hydrolysis + hydroxylation (indazole) | 4.84 | 366.182 4 | 366.182 4 | 0 | C18H24FN3O4 | 267, 161, 320, 249, 229, 193 | 4.0×107 | 4 |
| M6 | ester hydrolysis | 6.29 | 350.187 5 | 350.186 8 | -2.0 | C18H24FN3O3 | 233, 304, 251, 145, 213, 177 | 3.1×109 | 1 |
| M7 | Ester hydrolysis + oxidative defluorination | 3.56 | 348.191 8 | 348.191 3 | -1.4 | C18H25N3O4 | 213, 302, 231, 145 | 9.9×107 | 2 |
| M8 | Ester hydrolysis + oxidative defluorination + carboxylation | 3.49 | 362.171 1 | 362.170 5 | -1.7 | C18H23N3O5 | 217, 316, 227, 245 | 8.6×106 | 6 |
| M9 | Oxidative defluorination to pentanoic acid | 5.19 | 376.186 7 | 376.186 3 | -1.1 | C19H25N3O5 | 217, 227, 316, 245, 358 | 7.1×106 | 8 |
), ArticleFig(id=1218968418708017465, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1218263516671295821, language=CN, label=Table 1, caption=
Identification of 5F-AMB metabolites after 1 h incubation with human liver microsomes. NA: Not applicable
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| Peak ID | Metabolic reaction | RT /min | Exact mass [M+H]+(m/z) | Accurate mass [M+H]+(m/z) | Mass error /ppm | Chemical formula | Fragment ion | Area | Rank |
| 5F-AMB | NA | 8.24 | 364.203 1 | 364.202 5 | -1.7 | C19H26FN3O3 | 251, 304, 233, 213, 145, 177, 163 | 9.9×106 | |
| M1 | Hydroxylation (pentyl) | 5.84 | 380.198 0 | 380.197 9 | -0.4 | C19H26FN3O4 | 251, 362, 145, 213, 330, 163 | 8.5×105 | 9 |
| M2 | Ester hydrolysis + hydroxylation (pentyl) | 3.49 | 366.182 4 | 366.181 7 | -1.9 | C18H24FN3O4 | 267, 145, 320 | 5.7×107 | 3 |
| M3 | Ester hydrolysis + hydroxylation (butane moiety) | 3.90 | 366.182 4 | 366.181 9 | -1.3 | C18H24FN3O4 | 251, 145, 233, 348 | 7.9×106 | 7 |
| M4 | | 4.25 | 366.182 4 | 366.181 9 | -1.3 | C18H24FN3O4 | 251, 348, 145, 233, 213, 330, 177 | 1.2×107 | 5 |
| M5 | Ester hydrolysis + hydroxylation (indazole) | 4.84 | 366.182 4 | 366.182 4 | 0 | C18H24FN3O4 | 267, 161, 320, 249, 229, 193 | 4.0×107 | 4 |
| M6 | ester hydrolysis | 6.29 | 350.187 5 | 350.186 8 | -2.0 | C18H24FN3O3 | 233, 304, 251, 145, 213, 177 | 3.1×109 | 1 |
| M7 | Ester hydrolysis + oxidative defluorination | 3.56 | 348.191 8 | 348.191 3 | -1.4 | C18H25N3O4 | 213, 302, 231, 145 | 9.9×107 | 2 |
| M8 | Ester hydrolysis + oxidative defluorination + carboxylation | 3.49 | 362.171 1 | 362.170 5 | -1.7 | C18H23N3O5 | 217, 316, 227, 245 | 8.6×106 | 6 |
| M9 | Oxidative defluorination to pentanoic acid | 5.19 | 376.186 7 | 376.186 3 | -1.1 | C19H25N3O5 | 217, 227, 316, 245, 358 | 7.1×106 | 8 |
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