Simultaneous measurement of intracellular triphosphate metabolites of zidovudine, lamivudine and abacavir (carbovir) in human peripheral blood mononuclear cells by combined anion exchange solid phase extraction and LC–MS/MS
All nucleoside reverse transcriptase inhibitors (NRTI) must first be metabolized to their triphosphate forms in order to be active against HIV. Zidovudine (ZDV), abacavir (ABC) and lamivudine (3TC) have proven to be an efficacious combination. In order simultaneously to measure intracellular levels...
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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, 2007-05, Vol.850 (1), p.310-317 |
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container_title | Journal of chromatography. B, Analytical technologies in the biomedical and life sciences |
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creator | Robbins, Brian L. Poston, Philip A. Neal, Erin F. Slaughter, Clive Rodman, John H. |
description | All nucleoside reverse transcriptase inhibitors (NRTI) must first be metabolized to their triphosphate forms in order to be active against HIV. Zidovudine (ZDV), abacavir (ABC) and lamivudine (3TC) have proven to be an efficacious combination. In order simultaneously to measure intracellular levels of the triphosphates (-TP) of ZDV, ABC (carbovir, CBV) and 3TC, either together or individually, we have developed a cartridge-LC–MS/MS method. The quantitation range was 2.5–250
pg/μl for 3TC-TP, 0.1–10.0
pg/μl for ZDV-TP and 0.05–5.00
pg/μl for CBV-TP. This corresponds to 0.1–11.0
pmol 3TC-TP per million cells, 4–375
fmol ZDV-TP per million cells and 2–200
fmol CBV-TP per million cells, extracted from 10 million cells. Patient samples demonstrated measured levels in the middle regions of our standard curves both at pre-dose and 4
h post-dose times. |
doi_str_mv | 10.1016/j.jchromb.2006.12.015 |
format | Article |
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pg/μl for 3TC-TP, 0.1–10.0
pg/μl for ZDV-TP and 0.05–5.00
pg/μl for CBV-TP. This corresponds to 0.1–11.0
pmol 3TC-TP per million cells, 4–375
fmol ZDV-TP per million cells and 2–200
fmol CBV-TP per million cells, extracted from 10 million cells. Patient samples demonstrated measured levels in the middle regions of our standard curves both at pre-dose and 4
h post-dose times.</description><identifier>ISSN: 1570-0232</identifier><identifier>EISSN: 1873-376X</identifier><identifier>DOI: 10.1016/j.jchromb.2006.12.015</identifier><identifier>PMID: 17197254</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Analysis ; Analytical, structural and metabolic biochemistry ; Antiviral drug metabolism ; Biological and medical sciences ; Carbovir triphosphate ; Chromatography, High Pressure Liquid - methods ; Dideoxynucleosides - blood ; Fundamental and applied biological sciences. Psychology ; General pharmacology ; HIV Infections - blood ; Human immunodeficiency virus ; Humans ; Lamivudine - blood ; Lamivudine triphosphate ; Medical sciences ; Pharmacology. Drug treatments ; Phosphates - blood ; Reference Standards ; Reverse Transcriptase Inhibitors - blood ; Tandem Mass Spectrometry - methods ; Zidovudine - blood ; Zidovudine triphosphate</subject><ispartof>Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2007-05, Vol.850 (1), p.310-317</ispartof><rights>2006 Elsevier B.V.</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-270efb9e9f6458abaa37e709f321f6c84febb126e44b37e0e75e47200977245b3</citedby><cites>FETCH-LOGICAL-c422t-270efb9e9f6458abaa37e709f321f6c84febb126e44b37e0e75e47200977245b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jchromb.2006.12.015$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18738407$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17197254$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Robbins, Brian L.</creatorcontrib><creatorcontrib>Poston, Philip A.</creatorcontrib><creatorcontrib>Neal, Erin F.</creatorcontrib><creatorcontrib>Slaughter, Clive</creatorcontrib><creatorcontrib>Rodman, John H.</creatorcontrib><title>Simultaneous measurement of intracellular triphosphate metabolites of zidovudine, lamivudine and abacavir (carbovir) in human peripheral blood mononuclear cells by combined anion exchange solid phase extraction and LC–MS/MS</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>All nucleoside reverse transcriptase inhibitors (NRTI) must first be metabolized to their triphosphate forms in order to be active against HIV. Zidovudine (ZDV), abacavir (ABC) and lamivudine (3TC) have proven to be an efficacious combination. In order simultaneously to measure intracellular levels of the triphosphates (-TP) of ZDV, ABC (carbovir, CBV) and 3TC, either together or individually, we have developed a cartridge-LC–MS/MS method. The quantitation range was 2.5–250
pg/μl for 3TC-TP, 0.1–10.0
pg/μl for ZDV-TP and 0.05–5.00
pg/μl for CBV-TP. This corresponds to 0.1–11.0
pmol 3TC-TP per million cells, 4–375
fmol ZDV-TP per million cells and 2–200
fmol CBV-TP per million cells, extracted from 10 million cells. Patient samples demonstrated measured levels in the middle regions of our standard curves both at pre-dose and 4
h post-dose times.</description><subject>Analysis</subject><subject>Analytical, structural and metabolic biochemistry</subject><subject>Antiviral drug metabolism</subject><subject>Biological and medical sciences</subject><subject>Carbovir triphosphate</subject><subject>Chromatography, High Pressure Liquid - methods</subject><subject>Dideoxynucleosides - blood</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>General pharmacology</subject><subject>HIV Infections - blood</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Lamivudine - blood</subject><subject>Lamivudine triphosphate</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Phosphates - blood</subject><subject>Reference Standards</subject><subject>Reverse Transcriptase Inhibitors - blood</subject><subject>Tandem Mass Spectrometry - methods</subject><subject>Zidovudine - blood</subject><subject>Zidovudine triphosphate</subject><issn>1570-0232</issn><issn>1873-376X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUk2P0zAQjRCIXQo_AeQLCCSatR0nbk4IVXxJXXEoSNws25lQV47dtZ2K5cR_4BfCL8FRIu2Rk0eeN2_ezJuieEpwSTBpro7lUR-CH1RJMW5KQktM6nvFJdnwal3x5tv9HNccrzGt6EXxKMYjxoRjXj0sLggnLac1uyz-7M0w2iQd-DGiAWQcAwzgEvI9Mi4FqcHa0cqAUjCng4-ng0yQkUkqb02COCF_ms6fx844eI2sHMwcI-k6JJXU8mwCeqllUD5HrzIxOoyDdOgEEykEaZGy3ndo8M67UVvIDafOEalbpPOYmS5zOeMdgh_6IN13QDEL6FAWFCF_TlrTlJ-67rZ_f_2-3l9d7x8XD3ppIzxZ3lXx9f27L9uP693nD5-2b3drzShNa8ox9KqFtm9YvcmiZcWB47avKOkbvWE9KEVoA4ypnMHAa2A8777lnLJaVavixcx7Cv5mhJjEYOI0wrxbwTFjjLZ1BtYzUAcfY4BenIIZZLgVBIvJW3EUi7di8lYQKrK3ue7Z0mBUA3R3VYuZGfB8Aciope2DdNrEO1y-jA3LB7Aq3sw4yOs4GwgiagNOQ2cC6CQ6b_4j5R-t38ye</recordid><startdate>20070501</startdate><enddate>20070501</enddate><creator>Robbins, Brian L.</creator><creator>Poston, Philip A.</creator><creator>Neal, Erin F.</creator><creator>Slaughter, Clive</creator><creator>Rodman, John H.</creator><general>Elsevier B.V</general><general>Elsevier Science</general><scope>IQODW</scope><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>20070501</creationdate><title>Simultaneous measurement of intracellular triphosphate metabolites of zidovudine, lamivudine and abacavir (carbovir) in human peripheral blood mononuclear cells by combined anion exchange solid phase extraction and LC–MS/MS</title><author>Robbins, Brian L. ; Poston, Philip A. ; Neal, Erin F. ; Slaughter, Clive ; Rodman, John H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-270efb9e9f6458abaa37e709f321f6c84febb126e44b37e0e75e47200977245b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Analysis</topic><topic>Analytical, structural and metabolic biochemistry</topic><topic>Antiviral drug metabolism</topic><topic>Biological and medical sciences</topic><topic>Carbovir triphosphate</topic><topic>Chromatography, High Pressure Liquid - methods</topic><topic>Dideoxynucleosides - blood</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>General pharmacology</topic><topic>HIV Infections - blood</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Lamivudine - blood</topic><topic>Lamivudine triphosphate</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Phosphates - blood</topic><topic>Reference Standards</topic><topic>Reverse Transcriptase Inhibitors - blood</topic><topic>Tandem Mass Spectrometry - methods</topic><topic>Zidovudine - blood</topic><topic>Zidovudine triphosphate</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Robbins, Brian L.</creatorcontrib><creatorcontrib>Poston, Philip A.</creatorcontrib><creatorcontrib>Neal, Erin F.</creatorcontrib><creatorcontrib>Slaughter, Clive</creatorcontrib><creatorcontrib>Rodman, John H.</creatorcontrib><collection>Pascal-Francis</collection><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>Journal of chromatography. 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pg/μl for 3TC-TP, 0.1–10.0
pg/μl for ZDV-TP and 0.05–5.00
pg/μl for CBV-TP. This corresponds to 0.1–11.0
pmol 3TC-TP per million cells, 4–375
fmol ZDV-TP per million cells and 2–200
fmol CBV-TP per million cells, extracted from 10 million cells. Patient samples demonstrated measured levels in the middle regions of our standard curves both at pre-dose and 4
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subjects | Analysis Analytical, structural and metabolic biochemistry Antiviral drug metabolism Biological and medical sciences Carbovir triphosphate Chromatography, High Pressure Liquid - methods Dideoxynucleosides - blood Fundamental and applied biological sciences. Psychology General pharmacology HIV Infections - blood Human immunodeficiency virus Humans Lamivudine - blood Lamivudine triphosphate Medical sciences Pharmacology. Drug treatments Phosphates - blood Reference Standards Reverse Transcriptase Inhibitors - blood Tandem Mass Spectrometry - methods Zidovudine - blood Zidovudine triphosphate |
title | Simultaneous measurement of intracellular triphosphate metabolites of zidovudine, lamivudine and abacavir (carbovir) in human peripheral blood mononuclear cells by combined anion exchange solid phase extraction and LC–MS/MS |
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