An LC-MS/MS based candidate reference method for the quantification of total gentamicin in human serum and plasma using NMR characterized calibrator material
Accurate measurement of gentamicin concentration in serum and plasma is required for therapeutic drug monitoring to ensure appropriate treatment of patients. In this work, we present a validated LC-MS/MS-based candidate reference measurement procedure for total gentamicin quantification to be used f...
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| Veröffentlicht in: | Clinica chimica acta 2017-01, Vol.464, p.211-217 |
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| creator | Lucha, Stephanie Taibon, Judith Pongratz, Stephan Geletneky, Christian Huber, Erasmus Wintterle-Roehm, Christine Lang, Robert Grimm, Stefanie H. Duelffer, Thomas Tarasov, Kirill Zander, Johannes Vogeser, Michael Kobold, Uwe |
| description | Accurate measurement of gentamicin concentration in serum and plasma is required for therapeutic drug monitoring to ensure appropriate treatment of patients. In this work, we present a validated LC-MS/MS-based candidate reference measurement procedure for total gentamicin quantification to be used for standardization and harmonization of routine assays applied for therapeutic drug monitoring of this compound. Total gentamicin is the sum of the concentrations of five known congeners C1, C1a, C2, C2a and C2b. To our knowledge, there is so far no LC-MS method for quantification of total gentamicin in human serum described in literature.
Sample preparation was based on sample dilution with an aqueous internal standard solution followed by protein precipitation. Stable derivatives of gentamicin-glycine congeners were prepared by chemical synthesis and used as internal standards. The primary calibration material used in this assay was characterized by NMR spectroscopy and the pattern of the gentamicin congeners was determined. The total gentamicin was reported as the sum of the congeners which were quantified individually by LC-MS/MS.
The method allows the measurement of total gentamicin in human serum and plasma in the concentration range of 0.1 to 12.0μg/ml with an assay imprecision of ≤6% CV and an assay accuracy between 96% and 114%. LOD and LOQ for the total gentamicin were 0.04μg/ml and 0.13μg/ml, respectively. Comparative measurement of 128 native patient samples using this method implemented at two laboratory sites showed an excellent agreement.
Validation results proved that this protocol describes a robust and reliable method which is suggested as reference measurement procedure for the standardization and harmonization of routine assays for the quantification of total gentamicin.
•LC-MS/MS-based candidate reference method for total gentamicin quantification.•NMR characterization of the calibrator material.•quantification of individual congeners by quantitative NMR.•gentamicin-glycine based IS show identical chromatographic behaviour. |
| doi_str_mv | 10.1016/j.cca.2016.11.029 |
| format | Article |
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Sample preparation was based on sample dilution with an aqueous internal standard solution followed by protein precipitation. Stable derivatives of gentamicin-glycine congeners were prepared by chemical synthesis and used as internal standards. The primary calibration material used in this assay was characterized by NMR spectroscopy and the pattern of the gentamicin congeners was determined. The total gentamicin was reported as the sum of the congeners which were quantified individually by LC-MS/MS.
The method allows the measurement of total gentamicin in human serum and plasma in the concentration range of 0.1 to 12.0μg/ml with an assay imprecision of ≤6% CV and an assay accuracy between 96% and 114%. LOD and LOQ for the total gentamicin were 0.04μg/ml and 0.13μg/ml, respectively. Comparative measurement of 128 native patient samples using this method implemented at two laboratory sites showed an excellent agreement.
Validation results proved that this protocol describes a robust and reliable method which is suggested as reference measurement procedure for the standardization and harmonization of routine assays for the quantification of total gentamicin.
•LC-MS/MS-based candidate reference method for total gentamicin quantification.•NMR characterization of the calibrator material.•quantification of individual congeners by quantitative NMR.•gentamicin-glycine based IS show identical chromatographic behaviour.</description><identifier>ISSN: 0009-8981</identifier><identifier>EISSN: 1873-3492</identifier><identifier>DOI: 10.1016/j.cca.2016.11.029</identifier><identifier>PMID: 27871844</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Blood Chemical Analysis - standards ; Calibration ; Chromatography, Liquid ; Gentamicin ; Gentamicins - blood ; Humans ; LC-MS/MS ; Limit of Detection ; Linear Models ; Magnetic Resonance Spectroscopy - standards ; NMR ; Plasma ; Plasma - chemistry ; Reference method ; Reference Standards ; Serum ; Serum - chemistry ; Tandem Mass Spectrometry ; Uncertainty</subject><ispartof>Clinica chimica acta, 2017-01, Vol.464, p.211-217</ispartof><rights>2016</rights><rights>Copyright © 2016. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-af2fed362e67fa49f61002393c1f6484aa96a56023f05bda5e7fdaa1a0480ad03</citedby><cites>FETCH-LOGICAL-c353t-af2fed362e67fa49f61002393c1f6484aa96a56023f05bda5e7fdaa1a0480ad03</cites><orcidid>0000-0002-7527-1986</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0009898116304831$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27871844$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lucha, Stephanie</creatorcontrib><creatorcontrib>Taibon, Judith</creatorcontrib><creatorcontrib>Pongratz, Stephan</creatorcontrib><creatorcontrib>Geletneky, Christian</creatorcontrib><creatorcontrib>Huber, Erasmus</creatorcontrib><creatorcontrib>Wintterle-Roehm, Christine</creatorcontrib><creatorcontrib>Lang, Robert</creatorcontrib><creatorcontrib>Grimm, Stefanie H.</creatorcontrib><creatorcontrib>Duelffer, Thomas</creatorcontrib><creatorcontrib>Tarasov, Kirill</creatorcontrib><creatorcontrib>Zander, Johannes</creatorcontrib><creatorcontrib>Vogeser, Michael</creatorcontrib><creatorcontrib>Kobold, Uwe</creatorcontrib><title>An LC-MS/MS based candidate reference method for the quantification of total gentamicin in human serum and plasma using NMR characterized calibrator material</title><title>Clinica chimica acta</title><addtitle>Clin Chim Acta</addtitle><description>Accurate measurement of gentamicin concentration in serum and plasma is required for therapeutic drug monitoring to ensure appropriate treatment of patients. In this work, we present a validated LC-MS/MS-based candidate reference measurement procedure for total gentamicin quantification to be used for standardization and harmonization of routine assays applied for therapeutic drug monitoring of this compound. Total gentamicin is the sum of the concentrations of five known congeners C1, C1a, C2, C2a and C2b. To our knowledge, there is so far no LC-MS method for quantification of total gentamicin in human serum described in literature.
Sample preparation was based on sample dilution with an aqueous internal standard solution followed by protein precipitation. Stable derivatives of gentamicin-glycine congeners were prepared by chemical synthesis and used as internal standards. The primary calibration material used in this assay was characterized by NMR spectroscopy and the pattern of the gentamicin congeners was determined. The total gentamicin was reported as the sum of the congeners which were quantified individually by LC-MS/MS.
The method allows the measurement of total gentamicin in human serum and plasma in the concentration range of 0.1 to 12.0μg/ml with an assay imprecision of ≤6% CV and an assay accuracy between 96% and 114%. LOD and LOQ for the total gentamicin were 0.04μg/ml and 0.13μg/ml, respectively. Comparative measurement of 128 native patient samples using this method implemented at two laboratory sites showed an excellent agreement.
Validation results proved that this protocol describes a robust and reliable method which is suggested as reference measurement procedure for the standardization and harmonization of routine assays for the quantification of total gentamicin.
•LC-MS/MS-based candidate reference method for total gentamicin quantification.•NMR characterization of the calibrator material.•quantification of individual congeners by quantitative NMR.•gentamicin-glycine based IS show identical chromatographic behaviour.</description><subject>Blood Chemical Analysis - standards</subject><subject>Calibration</subject><subject>Chromatography, Liquid</subject><subject>Gentamicin</subject><subject>Gentamicins - blood</subject><subject>Humans</subject><subject>LC-MS/MS</subject><subject>Limit of Detection</subject><subject>Linear Models</subject><subject>Magnetic Resonance Spectroscopy - standards</subject><subject>NMR</subject><subject>Plasma</subject><subject>Plasma - chemistry</subject><subject>Reference method</subject><subject>Reference Standards</subject><subject>Serum</subject><subject>Serum - chemistry</subject><subject>Tandem Mass Spectrometry</subject><subject>Uncertainty</subject><issn>0009-8981</issn><issn>1873-3492</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFu1DAQhi0EokvhAbggH7kktZOsk4hTtQKKtAsShbM1a4-7XsX21naQ4F141zps4YhkyZ7RP__I_0fIa85qzri4OtZKQd2UZ815zZrxCVnxoW-rthubp2TFGBurYRz4BXmR0rGUHRP8Oblo-qHnQ9etyO9rT7eband7tbule0ioqQKvrYaMNKLBiF4hdZgPQVMTIs0HpPcz-GyNVZBt8DQYmkOGid6hz-Cssp6Wc5gdeJowzo4WT3qaIDmgc7L-jn7efaXqABFUxmh__dk72X2EXHY4WJowvSTPDEwJXz3el-T7h_ffNjfV9svHT5vrbaXadZsrMI1B3YoGRW-gG43gjDXt2CpuRDd0AKOAtSgtw9Z7DWvsjQbgwLqBgWbtJXl79j3FcD9jytLZpHCawGOYkyxZNWJJkxcpP0tVDCmVhOQpWgfxp-RMLlTkURYqcqEiOZeFSpl582g_7x3qfxN_MRTBu7MAyyd_WIwyKbsEr21ElaUO9j_2D6-QnzU</recordid><startdate>201701</startdate><enddate>201701</enddate><creator>Lucha, Stephanie</creator><creator>Taibon, Judith</creator><creator>Pongratz, Stephan</creator><creator>Geletneky, Christian</creator><creator>Huber, Erasmus</creator><creator>Wintterle-Roehm, Christine</creator><creator>Lang, Robert</creator><creator>Grimm, Stefanie H.</creator><creator>Duelffer, Thomas</creator><creator>Tarasov, Kirill</creator><creator>Zander, Johannes</creator><creator>Vogeser, Michael</creator><creator>Kobold, Uwe</creator><general>Elsevier B.V</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><orcidid>https://orcid.org/0000-0002-7527-1986</orcidid></search><sort><creationdate>201701</creationdate><title>An LC-MS/MS based candidate reference method for the quantification of total gentamicin in human serum and plasma using NMR characterized calibrator material</title><author>Lucha, Stephanie ; Taibon, Judith ; Pongratz, Stephan ; Geletneky, Christian ; Huber, Erasmus ; Wintterle-Roehm, Christine ; Lang, Robert ; Grimm, Stefanie H. ; Duelffer, Thomas ; Tarasov, Kirill ; Zander, Johannes ; Vogeser, Michael ; Kobold, Uwe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-af2fed362e67fa49f61002393c1f6484aa96a56023f05bda5e7fdaa1a0480ad03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Blood Chemical Analysis - standards</topic><topic>Calibration</topic><topic>Chromatography, Liquid</topic><topic>Gentamicin</topic><topic>Gentamicins - blood</topic><topic>Humans</topic><topic>LC-MS/MS</topic><topic>Limit of Detection</topic><topic>Linear Models</topic><topic>Magnetic Resonance Spectroscopy - standards</topic><topic>NMR</topic><topic>Plasma</topic><topic>Plasma - chemistry</topic><topic>Reference method</topic><topic>Reference Standards</topic><topic>Serum</topic><topic>Serum - chemistry</topic><topic>Tandem Mass Spectrometry</topic><topic>Uncertainty</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lucha, Stephanie</creatorcontrib><creatorcontrib>Taibon, Judith</creatorcontrib><creatorcontrib>Pongratz, Stephan</creatorcontrib><creatorcontrib>Geletneky, Christian</creatorcontrib><creatorcontrib>Huber, Erasmus</creatorcontrib><creatorcontrib>Wintterle-Roehm, Christine</creatorcontrib><creatorcontrib>Lang, Robert</creatorcontrib><creatorcontrib>Grimm, Stefanie H.</creatorcontrib><creatorcontrib>Duelffer, Thomas</creatorcontrib><creatorcontrib>Tarasov, Kirill</creatorcontrib><creatorcontrib>Zander, Johannes</creatorcontrib><creatorcontrib>Vogeser, Michael</creatorcontrib><creatorcontrib>Kobold, Uwe</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>Clinica chimica acta</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lucha, Stephanie</au><au>Taibon, Judith</au><au>Pongratz, Stephan</au><au>Geletneky, Christian</au><au>Huber, Erasmus</au><au>Wintterle-Roehm, Christine</au><au>Lang, Robert</au><au>Grimm, Stefanie H.</au><au>Duelffer, Thomas</au><au>Tarasov, Kirill</au><au>Zander, Johannes</au><au>Vogeser, Michael</au><au>Kobold, Uwe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An LC-MS/MS based candidate reference method for the quantification of total gentamicin in human serum and plasma using NMR characterized calibrator material</atitle><jtitle>Clinica chimica acta</jtitle><addtitle>Clin Chim Acta</addtitle><date>2017-01</date><risdate>2017</risdate><volume>464</volume><spage>211</spage><epage>217</epage><pages>211-217</pages><issn>0009-8981</issn><eissn>1873-3492</eissn><abstract>Accurate measurement of gentamicin concentration in serum and plasma is required for therapeutic drug monitoring to ensure appropriate treatment of patients. In this work, we present a validated LC-MS/MS-based candidate reference measurement procedure for total gentamicin quantification to be used for standardization and harmonization of routine assays applied for therapeutic drug monitoring of this compound. Total gentamicin is the sum of the concentrations of five known congeners C1, C1a, C2, C2a and C2b. To our knowledge, there is so far no LC-MS method for quantification of total gentamicin in human serum described in literature.
Sample preparation was based on sample dilution with an aqueous internal standard solution followed by protein precipitation. Stable derivatives of gentamicin-glycine congeners were prepared by chemical synthesis and used as internal standards. The primary calibration material used in this assay was characterized by NMR spectroscopy and the pattern of the gentamicin congeners was determined. The total gentamicin was reported as the sum of the congeners which were quantified individually by LC-MS/MS.
The method allows the measurement of total gentamicin in human serum and plasma in the concentration range of 0.1 to 12.0μg/ml with an assay imprecision of ≤6% CV and an assay accuracy between 96% and 114%. LOD and LOQ for the total gentamicin were 0.04μg/ml and 0.13μg/ml, respectively. Comparative measurement of 128 native patient samples using this method implemented at two laboratory sites showed an excellent agreement.
Validation results proved that this protocol describes a robust and reliable method which is suggested as reference measurement procedure for the standardization and harmonization of routine assays for the quantification of total gentamicin.
•LC-MS/MS-based candidate reference method for total gentamicin quantification.•NMR characterization of the calibrator material.•quantification of individual congeners by quantitative NMR.•gentamicin-glycine based IS show identical chromatographic behaviour.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>27871844</pmid><doi>10.1016/j.cca.2016.11.029</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-7527-1986</orcidid></addata></record> |
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| subjects | Blood Chemical Analysis - standards Calibration Chromatography, Liquid Gentamicin Gentamicins - blood Humans LC-MS/MS Limit of Detection Linear Models Magnetic Resonance Spectroscopy - standards NMR Plasma Plasma - chemistry Reference method Reference Standards Serum Serum - chemistry Tandem Mass Spectrometry Uncertainty |
| title | An LC-MS/MS based candidate reference method for the quantification of total gentamicin in human serum and plasma using NMR characterized calibrator material |
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