A high-throughput hydrophilic interaction liquid chromatography coupled with a charged aerosol detector method to assess trisulfides in IgG1 monoclonal antibodies using tris(2-carboxyethyl)phosphine reaction products: Tris(2-carboxyethyl)phosphine-oxide and tris(2-carboxyethyl)phosphine-sulfide
•A chromatographic HILICCAD method to measure levels of mAb trisulfide modifications.•Comparable results to the alternative method—peptide map with LC/MS detection.•Method applicable to cysteine-linked ADC production and cell culture process development. A robust, high-throughput method using hydrop...
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| Veröffentlicht in: | Journal of Chromatography A 2016-07, Vol.1457, p.107-115 |
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| creator | Cornell, Christopher Karanjit, Amish Chen, Yan Jacobson, Fredric |
| description | •A chromatographic HILICCAD method to measure levels of mAb trisulfide modifications.•Comparable results to the alternative method—peptide map with LC/MS detection.•Method applicable to cysteine-linked ADC production and cell culture process development.
A robust, high-throughput method using hydrophilic interaction liquid chromatography (HILIC) coupled with a charged aerosol detector (CAD) is reported as a novel approach for trisulfide quantitation in monoclonal antibodies (mAbs). The products of mAb reduction using tris(2-carboxyethyl)phosphine (TCEP) include a species (TCEP(S)) that is stoichiometrically produced from trisulfides. The TCEP reaction products are chromatographically separated, detected, and quantified by the HILICCAD method. The method was qualified to quantify trisulfides across a range of 1–40% (mol trisulfide/mol mAb). In all tested matrix components, assay linearity and intermediate precision were established with correlation coefficients (R2)>0.99, and relative standard deviations (RSD) |
| doi_str_mv | 10.1016/j.chroma.2016.06.037 |
| format | Article |
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A robust, high-throughput method using hydrophilic interaction liquid chromatography (HILIC) coupled with a charged aerosol detector (CAD) is reported as a novel approach for trisulfide quantitation in monoclonal antibodies (mAbs). The products of mAb reduction using tris(2-carboxyethyl)phosphine (TCEP) include a species (TCEP(S)) that is stoichiometrically produced from trisulfides. The TCEP reaction products are chromatographically separated, detected, and quantified by the HILICCAD method. The method was qualified to quantify trisulfides across a range of 1–40% (mol trisulfide/mol mAb). In all tested matrix components, assay linearity and intermediate precision were established with correlation coefficients (R2)>0.99, and relative standard deviations (RSD)<10%. A method comparability study was performed using peptide mapping LC–MS as an orthogonal measurement. For the range of 1–40% trisulfides, the analysis demonstrates that, on average, HILICCAD reads between 0.95 and 1.10 times the value of LC–MS with 95% confidence. Applications of the HILICCAD method include trisulfide determination in purified mAbs to be used in the production of cysteine-linked antibody-drug conjugates, and in cell culture development studies to understand sources of, and strategies for control of, trisulfides.</description><identifier>ISSN: 0021-9673</identifier><identifier>EISSN: 1873-3778</identifier><identifier>DOI: 10.1016/j.chroma.2016.06.037</identifier><identifier>PMID: 27345209</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Aerosols ; Antibodies, Monoclonal - chemistry ; Antibody-drug conjugates ; Bonding ; Charged aerosol detector ; Chromatography ; Chromatography, Liquid ; Confidence intervals ; Cysteine - chemistry ; Detectors ; Hydrophilic interaction chromatography ; Hydrophobic and Hydrophilic Interactions ; Immunoglobulin G - chemistry ; Liquid chromatography ; Mass Spectrometry ; Monoclonal antibodies ; Oxidation-Reduction ; Phosphines - chemistry ; Reaction products ; Sulfides - analysis ; Tris(2-carboxyethyl)phosphine (TCEP) ; Tris(2-carboxyethyl)phosphine-oxide (TCEP[O]) ; Tris(2-carboxyethyl)phosphine-sulfide (TCEP[S]) ; Trisulfides</subject><ispartof>Journal of Chromatography A, 2016-07, Vol.1457, p.107-115</ispartof><rights>2016 Elsevier B.V.</rights><rights>Copyright © 2016 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-c158d80af06635cccdd1054169b5fea67d8cede31e0f74fc13f8d245cceeb81e3</citedby><cites>FETCH-LOGICAL-c428t-c158d80af06635cccdd1054169b5fea67d8cede31e0f74fc13f8d245cceeb81e3</cites><orcidid>0000-0001-9603-2901</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.chroma.2016.06.037$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27345209$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cornell, Christopher</creatorcontrib><creatorcontrib>Karanjit, Amish</creatorcontrib><creatorcontrib>Chen, Yan</creatorcontrib><creatorcontrib>Jacobson, Fredric</creatorcontrib><title>A high-throughput hydrophilic interaction liquid chromatography coupled with a charged aerosol detector method to assess trisulfides in IgG1 monoclonal antibodies using tris(2-carboxyethyl)phosphine reaction products: Tris(2-carboxyethyl)phosphine-oxide and tris(2-carboxyethyl)phosphine-sulfide</title><title>Journal of Chromatography A</title><addtitle>J Chromatogr A</addtitle><description>•A chromatographic HILICCAD method to measure levels of mAb trisulfide modifications.•Comparable results to the alternative method—peptide map with LC/MS detection.•Method applicable to cysteine-linked ADC production and cell culture process development.
A robust, high-throughput method using hydrophilic interaction liquid chromatography (HILIC) coupled with a charged aerosol detector (CAD) is reported as a novel approach for trisulfide quantitation in monoclonal antibodies (mAbs). The products of mAb reduction using tris(2-carboxyethyl)phosphine (TCEP) include a species (TCEP(S)) that is stoichiometrically produced from trisulfides. The TCEP reaction products are chromatographically separated, detected, and quantified by the HILICCAD method. The method was qualified to quantify trisulfides across a range of 1–40% (mol trisulfide/mol mAb). In all tested matrix components, assay linearity and intermediate precision were established with correlation coefficients (R2)>0.99, and relative standard deviations (RSD)<10%. A method comparability study was performed using peptide mapping LC–MS as an orthogonal measurement. For the range of 1–40% trisulfides, the analysis demonstrates that, on average, HILICCAD reads between 0.95 and 1.10 times the value of LC–MS with 95% confidence. Applications of the HILICCAD method include trisulfide determination in purified mAbs to be used in the production of cysteine-linked antibody-drug conjugates, and in cell culture development studies to understand sources of, and strategies for control of, trisulfides.</description><subject>Aerosols</subject><subject>Antibodies, Monoclonal - chemistry</subject><subject>Antibody-drug conjugates</subject><subject>Bonding</subject><subject>Charged aerosol detector</subject><subject>Chromatography</subject><subject>Chromatography, Liquid</subject><subject>Confidence intervals</subject><subject>Cysteine - chemistry</subject><subject>Detectors</subject><subject>Hydrophilic interaction chromatography</subject><subject>Hydrophobic and Hydrophilic Interactions</subject><subject>Immunoglobulin G - chemistry</subject><subject>Liquid chromatography</subject><subject>Mass Spectrometry</subject><subject>Monoclonal antibodies</subject><subject>Oxidation-Reduction</subject><subject>Phosphines - chemistry</subject><subject>Reaction products</subject><subject>Sulfides - analysis</subject><subject>Tris(2-carboxyethyl)phosphine (TCEP)</subject><subject>Tris(2-carboxyethyl)phosphine-oxide (TCEP[O])</subject><subject>Tris(2-carboxyethyl)phosphine-sulfide (TCEP[S])</subject><subject>Trisulfides</subject><issn>0021-9673</issn><issn>1873-3778</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUsFu1DAQDQhEl8IfIOQb5ZDFjpPY2wNSVZVSqRKXcrYce5J45cSp7UDz9_WSheMKaSRrNG_ee-OZLPtA8JZgUn_Zb1Xv3SC3Rcq2OAVlL7MN4YzmlDH-KttgXJB8VzN6lr0NYY8xYZgVb7KzgtGyKvBu8-LTFepN1-cxcc1dP80R9Yv2buqNNQqZMYKXKho3ImseZ6PRqhpd5-XUL0i5ebKg0W8TeyRTVfoupRK8C84iDRFUdB4NEHunUXRIhgAhoOhNmG1rNIQkg-66W4IGNzpl3SgtkmM0jdMmVedgxu4P_qLIlfSNe1oS22I_T70LyekIyMPR5eSdnlUMl-jhVEPunpJyUtGnifOjx3fZ61baAO-P73n289vNw_X3_P7H7d311X2uyoLHXJGKa45li-uaVkoprQmuSlLvmqoFWTPNFWigBHDLylYR2nJdlAkJ0HAC9Dy7WHnTHI8zhCgGExRYK0dwcxCE06quSEnr_4ASwjkvqgO0XKEqbSV4aMXkzSD9IggWh2sSe7HuVRyuSeAUlKW2j0eFuRlA_2v6ez4J8HUFQPqSXwa8CMrAmEY0Pq1daGdOKzwDWo7oIQ</recordid><startdate>20160729</startdate><enddate>20160729</enddate><creator>Cornell, Christopher</creator><creator>Karanjit, Amish</creator><creator>Chen, Yan</creator><creator>Jacobson, Fredric</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>7ST</scope><scope>C1K</scope><scope>SOI</scope><scope>7U5</scope><scope>8FD</scope><scope>L7M</scope><orcidid>https://orcid.org/0000-0001-9603-2901</orcidid></search><sort><creationdate>20160729</creationdate><title>A high-throughput hydrophilic interaction liquid chromatography coupled with a charged aerosol detector method to assess trisulfides in IgG1 monoclonal antibodies using tris(2-carboxyethyl)phosphine reaction products: Tris(2-carboxyethyl)phosphine-oxide and tris(2-carboxyethyl)phosphine-sulfide</title><author>Cornell, Christopher ; Karanjit, Amish ; Chen, Yan ; Jacobson, Fredric</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-c158d80af06635cccdd1054169b5fea67d8cede31e0f74fc13f8d245cceeb81e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Aerosols</topic><topic>Antibodies, Monoclonal - chemistry</topic><topic>Antibody-drug conjugates</topic><topic>Bonding</topic><topic>Charged aerosol detector</topic><topic>Chromatography</topic><topic>Chromatography, Liquid</topic><topic>Confidence intervals</topic><topic>Cysteine - chemistry</topic><topic>Detectors</topic><topic>Hydrophilic interaction chromatography</topic><topic>Hydrophobic and Hydrophilic Interactions</topic><topic>Immunoglobulin G - chemistry</topic><topic>Liquid chromatography</topic><topic>Mass Spectrometry</topic><topic>Monoclonal antibodies</topic><topic>Oxidation-Reduction</topic><topic>Phosphines - chemistry</topic><topic>Reaction products</topic><topic>Sulfides - analysis</topic><topic>Tris(2-carboxyethyl)phosphine (TCEP)</topic><topic>Tris(2-carboxyethyl)phosphine-oxide (TCEP[O])</topic><topic>Tris(2-carboxyethyl)phosphine-sulfide (TCEP[S])</topic><topic>Trisulfides</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cornell, Christopher</creatorcontrib><creatorcontrib>Karanjit, Amish</creatorcontrib><creatorcontrib>Chen, Yan</creatorcontrib><creatorcontrib>Jacobson, Fredric</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Environment Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Technology Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Journal of Chromatography A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cornell, Christopher</au><au>Karanjit, Amish</au><au>Chen, Yan</au><au>Jacobson, Fredric</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A high-throughput hydrophilic interaction liquid chromatography coupled with a charged aerosol detector method to assess trisulfides in IgG1 monoclonal antibodies using tris(2-carboxyethyl)phosphine reaction products: Tris(2-carboxyethyl)phosphine-oxide and tris(2-carboxyethyl)phosphine-sulfide</atitle><jtitle>Journal of Chromatography A</jtitle><addtitle>J Chromatogr A</addtitle><date>2016-07-29</date><risdate>2016</risdate><volume>1457</volume><spage>107</spage><epage>115</epage><pages>107-115</pages><issn>0021-9673</issn><eissn>1873-3778</eissn><abstract>•A chromatographic HILICCAD method to measure levels of mAb trisulfide modifications.•Comparable results to the alternative method—peptide map with LC/MS detection.•Method applicable to cysteine-linked ADC production and cell culture process development.
A robust, high-throughput method using hydrophilic interaction liquid chromatography (HILIC) coupled with a charged aerosol detector (CAD) is reported as a novel approach for trisulfide quantitation in monoclonal antibodies (mAbs). The products of mAb reduction using tris(2-carboxyethyl)phosphine (TCEP) include a species (TCEP(S)) that is stoichiometrically produced from trisulfides. The TCEP reaction products are chromatographically separated, detected, and quantified by the HILICCAD method. The method was qualified to quantify trisulfides across a range of 1–40% (mol trisulfide/mol mAb). In all tested matrix components, assay linearity and intermediate precision were established with correlation coefficients (R2)>0.99, and relative standard deviations (RSD)<10%. A method comparability study was performed using peptide mapping LC–MS as an orthogonal measurement. For the range of 1–40% trisulfides, the analysis demonstrates that, on average, HILICCAD reads between 0.95 and 1.10 times the value of LC–MS with 95% confidence. Applications of the HILICCAD method include trisulfide determination in purified mAbs to be used in the production of cysteine-linked antibody-drug conjugates, and in cell culture development studies to understand sources of, and strategies for control of, trisulfides.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>27345209</pmid><doi>10.1016/j.chroma.2016.06.037</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-9603-2901</orcidid></addata></record> |
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| identifier | ISSN: 0021-9673 |
| ispartof | Journal of Chromatography A, 2016-07, Vol.1457, p.107-115 |
| issn | 0021-9673 1873-3778 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Aerosols Antibodies, Monoclonal - chemistry Antibody-drug conjugates Bonding Charged aerosol detector Chromatography Chromatography, Liquid Confidence intervals Cysteine - chemistry Detectors Hydrophilic interaction chromatography Hydrophobic and Hydrophilic Interactions Immunoglobulin G - chemistry Liquid chromatography Mass Spectrometry Monoclonal antibodies Oxidation-Reduction Phosphines - chemistry Reaction products Sulfides - analysis Tris(2-carboxyethyl)phosphine (TCEP) Tris(2-carboxyethyl)phosphine-oxide (TCEP[O]) Tris(2-carboxyethyl)phosphine-sulfide (TCEP[S]) Trisulfides |
| title | A high-throughput hydrophilic interaction liquid chromatography coupled with a charged aerosol detector method to assess trisulfides in IgG1 monoclonal antibodies using tris(2-carboxyethyl)phosphine reaction products: Tris(2-carboxyethyl)phosphine-oxide and tris(2-carboxyethyl)phosphine-sulfide |
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