Stereoselective separation of omeprazole and 5-hydroxy-omeprazole using dried plasma spots and a heart-cutting 2D-LC approach for accurate CYP2C19 phenotyping
•Two dimensional LC-MS/MS method for precise omeprazole and metabolites enantiomers quantification in human plasma.•Fast and efficient separation, with a total runtime of less than 8 min.•Innovative 2D-LC minimizes carryover, extending chiral column lifetime.•Successfully applied to clinical samples...
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| Veröffentlicht in: | Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2024-01, Vol.1232, p.123962-123962, Article 123962 |
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| container_title | Journal of chromatography. B, Analytical technologies in the biomedical and life sciences |
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| creator | Abouir, Kenza Samer, Caroline Landry, Romain Varesio, Emmanuel Daali, Youssef |
| description | •Two dimensional LC-MS/MS method for precise omeprazole and metabolites enantiomers quantification in human plasma.•Fast and efficient separation, with a total runtime of less than 8 min.•Innovative 2D-LC minimizes carryover, extending chiral column lifetime.•Successfully applied to clinical samples, demonstrating its clinical utility.
Omeprazole (OME) is a widely used gastric proton pump inhibitor, marketed as a racemic mixture comprising (S)- and (R)-enantiomers, with distinct pharmacokinetic profiles. OME is primarily metabolized by the cytochrome P450 enzymes 2C19 (CYP2C19) and 3A4 (CYP3A4). OME is a conventional probe for CYP2C19 phenotyping. Accurate measurement of these enantiomers and their metabolites is essential for pharmacokinetic studies. This article presents a sensitive and accurate two-dimensional liquid chromatography-mass spectrometry (LC-MS/MS) method for the simultaneous quantification of OME enantiomers and its hydroxylated metabolite (5-hydroxyomeprazole) in human plasma.
The method involves an online extraction using an achiral Discovery HS C18 trapping column for purification (20 × 2.1 mm ID, 5μm particle size, Supelco) and subsequent forward flush elution onto a chlorinated phenylcarbamate cellulose-based chiral column (150x2mm ID, 3 μm particle size, Lux Cellulose-4, Phenomenex). The assay was fully validated and met international validation criteria for accuracy, precision, and stability and ensured high selectivity and sensitivity within a short runtime ( |
| doi_str_mv | 10.1016/j.jchromb.2023.123962 |
| format | Article |
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Omeprazole (OME) is a widely used gastric proton pump inhibitor, marketed as a racemic mixture comprising (S)- and (R)-enantiomers, with distinct pharmacokinetic profiles. OME is primarily metabolized by the cytochrome P450 enzymes 2C19 (CYP2C19) and 3A4 (CYP3A4). OME is a conventional probe for CYP2C19 phenotyping. Accurate measurement of these enantiomers and their metabolites is essential for pharmacokinetic studies. This article presents a sensitive and accurate two-dimensional liquid chromatography-mass spectrometry (LC-MS/MS) method for the simultaneous quantification of OME enantiomers and its hydroxylated metabolite (5-hydroxyomeprazole) in human plasma.
The method involves an online extraction using an achiral Discovery HS C18 trapping column for purification (20 × 2.1 mm ID, 5μm particle size, Supelco) and subsequent forward flush elution onto a chlorinated phenylcarbamate cellulose-based chiral column (150x2mm ID, 3 μm particle size, Lux Cellulose-4, Phenomenex). The assay was fully validated and met international validation criteria for accuracy, precision, and stability and ensured high selectivity and sensitivity within a short runtime (<8 min). Application of this method to clinical samples demonstrated its utility in studying OME enantiomer pharmacokinetics, particularly its potential for phenotyping the activity of the CYP2C19 isoenzyme.
This robust analytical approach offers a valuable tool for clinicians and researchers studying OME's pharmacokinetics, providing insights into its metabolism and potential implications for personalized medicine.</description><identifier>ISSN: 1570-0232</identifier><identifier>EISSN: 1873-376X</identifier><identifier>DOI: 10.1016/j.jchromb.2023.123962</identifier><identifier>PMID: 38096743</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>5-Hydroxy-omeprazole ; cellulose ; CYP2C19 ; cytochrome P-450 ; enantiomers ; humans ; hydroxylation ; isozymes ; liquid chromatography ; mass spectrometry ; metabolites ; Omeprazole ; particle size ; pharmacokinetics ; Phenotype ; precision medicine ; proton pump inhibitors ; Stereoselective ; stereoselectivity</subject><ispartof>Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2024-01, Vol.1232, p.123962-123962, Article 123962</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2023 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c393t-7c12e4a8f7f4bcb7712fd2db777874e5a8697f80a79fa49e11de582d909a80da3</cites><orcidid>0000-0002-4401-432X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jchromb.2023.123962$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38096743$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abouir, Kenza</creatorcontrib><creatorcontrib>Samer, Caroline</creatorcontrib><creatorcontrib>Landry, Romain</creatorcontrib><creatorcontrib>Varesio, Emmanuel</creatorcontrib><creatorcontrib>Daali, Youssef</creatorcontrib><title>Stereoselective separation of omeprazole and 5-hydroxy-omeprazole using dried plasma spots and a heart-cutting 2D-LC approach for accurate CYP2C19 phenotyping</title><title>Journal of chromatography. B, Analytical technologies in the biomedical and life sciences</title><addtitle>J Chromatogr B Analyt Technol Biomed Life Sci</addtitle><description>•Two dimensional LC-MS/MS method for precise omeprazole and metabolites enantiomers quantification in human plasma.•Fast and efficient separation, with a total runtime of less than 8 min.•Innovative 2D-LC minimizes carryover, extending chiral column lifetime.•Successfully applied to clinical samples, demonstrating its clinical utility.
Omeprazole (OME) is a widely used gastric proton pump inhibitor, marketed as a racemic mixture comprising (S)- and (R)-enantiomers, with distinct pharmacokinetic profiles. OME is primarily metabolized by the cytochrome P450 enzymes 2C19 (CYP2C19) and 3A4 (CYP3A4). OME is a conventional probe for CYP2C19 phenotyping. Accurate measurement of these enantiomers and their metabolites is essential for pharmacokinetic studies. This article presents a sensitive and accurate two-dimensional liquid chromatography-mass spectrometry (LC-MS/MS) method for the simultaneous quantification of OME enantiomers and its hydroxylated metabolite (5-hydroxyomeprazole) in human plasma.
The method involves an online extraction using an achiral Discovery HS C18 trapping column for purification (20 × 2.1 mm ID, 5μm particle size, Supelco) and subsequent forward flush elution onto a chlorinated phenylcarbamate cellulose-based chiral column (150x2mm ID, 3 μm particle size, Lux Cellulose-4, Phenomenex). The assay was fully validated and met international validation criteria for accuracy, precision, and stability and ensured high selectivity and sensitivity within a short runtime (<8 min). Application of this method to clinical samples demonstrated its utility in studying OME enantiomer pharmacokinetics, particularly its potential for phenotyping the activity of the CYP2C19 isoenzyme.
This robust analytical approach offers a valuable tool for clinicians and researchers studying OME's pharmacokinetics, providing insights into its metabolism and potential implications for personalized medicine.</description><subject>5-Hydroxy-omeprazole</subject><subject>cellulose</subject><subject>CYP2C19</subject><subject>cytochrome P-450</subject><subject>enantiomers</subject><subject>humans</subject><subject>hydroxylation</subject><subject>isozymes</subject><subject>liquid chromatography</subject><subject>mass spectrometry</subject><subject>metabolites</subject><subject>Omeprazole</subject><subject>particle size</subject><subject>pharmacokinetics</subject><subject>Phenotype</subject><subject>precision medicine</subject><subject>proton pump inhibitors</subject><subject>Stereoselective</subject><subject>stereoselectivity</subject><issn>1570-0232</issn><issn>1873-376X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqFkU2r1DAUhoso3g_9CUqWbjrmo22alUjVqzCgoIKuwpnk1GZom5qkF8cf428144zi7q5y4Dxv3pCnKJ4wumGUNc_3m70Zgp92G0652DAuVMPvFZeslaIUsvlyP8-1pGXe8oviKsY9pUxSKR4WF6KlqpGVuCx-fUwY0Ecc0SR3iyTiAgGS8zPxPfETLgF--hEJzJbU5XCwwf84lP8t1ujmb8QGh5YsI8QJSFx8in8SQAaEkEqzpnTE-Kty2xFYluDBDKT3gYAxa25E0n39wDumyDLg7NNhyfyj4kEPY8TH5_O6-Pzm9afubbl9f_Oue7ktjVAildIwjhW0veyrndlJyXhvuc2DbGWFNbSNkn1LQaoeKoWMWaxbbhVV0FIL4rp4dro3v-v7ijHpyUWD4wgz-jVqwWrBaaXq5k6UK8pVXamGZbQ-oSb4GAP2eglugnDQjOqjRb3XZ4v6aFGfLObc03PFupvQ_kv91ZaBFycA85_cOgw6GoezQetC9qitd3dU_AYZyrLZ</recordid><startdate>20240101</startdate><enddate>20240101</enddate><creator>Abouir, Kenza</creator><creator>Samer, Caroline</creator><creator>Landry, Romain</creator><creator>Varesio, Emmanuel</creator><creator>Daali, Youssef</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0002-4401-432X</orcidid></search><sort><creationdate>20240101</creationdate><title>Stereoselective separation of omeprazole and 5-hydroxy-omeprazole using dried plasma spots and a heart-cutting 2D-LC approach for accurate CYP2C19 phenotyping</title><author>Abouir, Kenza ; Samer, Caroline ; Landry, Romain ; Varesio, Emmanuel ; Daali, Youssef</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-7c12e4a8f7f4bcb7712fd2db777874e5a8697f80a79fa49e11de582d909a80da3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>5-Hydroxy-omeprazole</topic><topic>cellulose</topic><topic>CYP2C19</topic><topic>cytochrome P-450</topic><topic>enantiomers</topic><topic>humans</topic><topic>hydroxylation</topic><topic>isozymes</topic><topic>liquid chromatography</topic><topic>mass spectrometry</topic><topic>metabolites</topic><topic>Omeprazole</topic><topic>particle size</topic><topic>pharmacokinetics</topic><topic>Phenotype</topic><topic>precision medicine</topic><topic>proton pump inhibitors</topic><topic>Stereoselective</topic><topic>stereoselectivity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abouir, Kenza</creatorcontrib><creatorcontrib>Samer, Caroline</creatorcontrib><creatorcontrib>Landry, Romain</creatorcontrib><creatorcontrib>Varesio, Emmanuel</creatorcontrib><creatorcontrib>Daali, Youssef</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Journal of chromatography. B, Analytical technologies in the biomedical and life sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abouir, Kenza</au><au>Samer, Caroline</au><au>Landry, Romain</au><au>Varesio, Emmanuel</au><au>Daali, Youssef</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stereoselective separation of omeprazole and 5-hydroxy-omeprazole using dried plasma spots and a heart-cutting 2D-LC approach for accurate CYP2C19 phenotyping</atitle><jtitle>Journal of chromatography. B, Analytical technologies in the biomedical and life sciences</jtitle><addtitle>J Chromatogr B Analyt Technol Biomed Life Sci</addtitle><date>2024-01-01</date><risdate>2024</risdate><volume>1232</volume><spage>123962</spage><epage>123962</epage><pages>123962-123962</pages><artnum>123962</artnum><issn>1570-0232</issn><eissn>1873-376X</eissn><abstract>•Two dimensional LC-MS/MS method for precise omeprazole and metabolites enantiomers quantification in human plasma.•Fast and efficient separation, with a total runtime of less than 8 min.•Innovative 2D-LC minimizes carryover, extending chiral column lifetime.•Successfully applied to clinical samples, demonstrating its clinical utility.
Omeprazole (OME) is a widely used gastric proton pump inhibitor, marketed as a racemic mixture comprising (S)- and (R)-enantiomers, with distinct pharmacokinetic profiles. OME is primarily metabolized by the cytochrome P450 enzymes 2C19 (CYP2C19) and 3A4 (CYP3A4). OME is a conventional probe for CYP2C19 phenotyping. Accurate measurement of these enantiomers and their metabolites is essential for pharmacokinetic studies. This article presents a sensitive and accurate two-dimensional liquid chromatography-mass spectrometry (LC-MS/MS) method for the simultaneous quantification of OME enantiomers and its hydroxylated metabolite (5-hydroxyomeprazole) in human plasma.
The method involves an online extraction using an achiral Discovery HS C18 trapping column for purification (20 × 2.1 mm ID, 5μm particle size, Supelco) and subsequent forward flush elution onto a chlorinated phenylcarbamate cellulose-based chiral column (150x2mm ID, 3 μm particle size, Lux Cellulose-4, Phenomenex). The assay was fully validated and met international validation criteria for accuracy, precision, and stability and ensured high selectivity and sensitivity within a short runtime (<8 min). Application of this method to clinical samples demonstrated its utility in studying OME enantiomer pharmacokinetics, particularly its potential for phenotyping the activity of the CYP2C19 isoenzyme.
This robust analytical approach offers a valuable tool for clinicians and researchers studying OME's pharmacokinetics, providing insights into its metabolism and potential implications for personalized medicine.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>38096743</pmid><doi>10.1016/j.jchromb.2023.123962</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-4401-432X</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Elsevier ScienceDirect Journals |
| subjects | 5-Hydroxy-omeprazole cellulose CYP2C19 cytochrome P-450 enantiomers humans hydroxylation isozymes liquid chromatography mass spectrometry metabolites Omeprazole particle size pharmacokinetics Phenotype precision medicine proton pump inhibitors Stereoselective stereoselectivity |
| title | Stereoselective separation of omeprazole and 5-hydroxy-omeprazole using dried plasma spots and a heart-cutting 2D-LC approach for accurate CYP2C19 phenotyping |
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