Analytical Characterization of an Orally-Delivered Peptide Pharmaceutical Product
The characterization of orally-delivered peptide pharmaceuticals presents several challenges to analytical methods in comparison to characterization of conventional small-molecule drugs. These challenges include the analysis and characterization of difficult-to-separate impurities, secondary structu...
Gespeichert in:
| Veröffentlicht in: | Analytical chemistry (Washington) 2012-05, Vol.84 (10), p.4357-4372 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 4372 |
|---|---|
| container_issue | 10 |
| container_start_page | 4357 |
| container_title | Analytical chemistry (Washington) |
| container_volume | 84 |
| creator | Kelley, Wayne P Chen, Shujun Floyd, Philip D Hu, Ping Kapsi, Shiva G Kord, Alireza S Sun, Mingjiang Vogt, Frederick G |
| description | The characterization of orally-delivered peptide pharmaceuticals presents several challenges to analytical methods in comparison to characterization of conventional small-molecule drugs. These challenges include the analysis and characterization of difficult-to-separate impurities, secondary structure, the amorphous solid-state form, and the integrity of enteric-coated drug delivery systems. This work presents the multidisciplinary analytical characterization of a parathyroid hormone (PTH) peptide active pharmaceutical ingredient (API) and an oral formulation of this API within enteric-coated sucrose spheres. The analysis of impurities and degradation products in API and formulated drug product was facilitated by the development of an ultrahigh-performance liquid chromatography (UHPLC) method for analysis by high-resolution mass spectrometry (MS). The use of UHPLC allowed for additional resolution needed to detect impurities and degradation products of interest. The secondary structure was probed using a combination of solution-state NMR, infrared, and circular dichroism spectroscopic methods. Solid-state NMR is used to detect amorphous API in a nondestructive manner directly within the coated sucrose sphere formulation. Fluorescence and Raman microscopy were used in conjunction with Raman mapping to show enteric coating integrity and observe the distribution of API beneath the enteric-coating on the sucrose spheres. The methods are combined in a multidisciplinary approach to characterize the quality of the enteric-coated peptide product. |
| doi_str_mv | 10.1021/ac203478r |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1013926829</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1013926829</sourcerecordid><originalsourceid>FETCH-LOGICAL-a373t-d7eb84a929cf677366a3a84991457a5c4f1c131a600ec3e68422f0ebe542dcee3</originalsourceid><addsrcrecordid>eNpd0VtLwzAUB_AgipvTB7-AFETQh2puTZrHMa8w2AR9LmfpKXZ07UxaYX56o5tT9pSXX87lfwg5ZfSaUc5uwHIqpE7dHumzhNNYpSnfJ31KqYi5prRHjryfU8oYZeqQ9DiXRkvF--R5WEO1aksLVTR6Awe2RVd-Qls2ddQUEdTRxEFVreJbrMoPdJhHU1y2ZY7RNPgFWOzW36euyTvbHpODAiqPJ5t3QF7v715Gj_F48vA0Go5jEFq0ca5xlkow3NhCaS2UAgGpNIbJRENiZcEsEwwUpWgFqlRyXlCcYSJ5bhHFgFyu6y5d896hb7NF6S1WFdTYdD4LqwrDVcpNoOc7dN50Liz-oxLFqeE6qKu1sq7x3mGRLV25ALcKKPvOOdvmHOzZpmI3W2C-lb_BBnCxAeBDOIWD2pb-zyUmHIPJPwfW_59qt-EXw9mPvA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1015620927</pqid></control><display><type>article</type><title>Analytical Characterization of an Orally-Delivered Peptide Pharmaceutical Product</title><source>MEDLINE</source><source>American Chemical Society Journals</source><creator>Kelley, Wayne P ; Chen, Shujun ; Floyd, Philip D ; Hu, Ping ; Kapsi, Shiva G ; Kord, Alireza S ; Sun, Mingjiang ; Vogt, Frederick G</creator><creatorcontrib>Kelley, Wayne P ; Chen, Shujun ; Floyd, Philip D ; Hu, Ping ; Kapsi, Shiva G ; Kord, Alireza S ; Sun, Mingjiang ; Vogt, Frederick G</creatorcontrib><description>The characterization of orally-delivered peptide pharmaceuticals presents several challenges to analytical methods in comparison to characterization of conventional small-molecule drugs. These challenges include the analysis and characterization of difficult-to-separate impurities, secondary structure, the amorphous solid-state form, and the integrity of enteric-coated drug delivery systems. This work presents the multidisciplinary analytical characterization of a parathyroid hormone (PTH) peptide active pharmaceutical ingredient (API) and an oral formulation of this API within enteric-coated sucrose spheres. The analysis of impurities and degradation products in API and formulated drug product was facilitated by the development of an ultrahigh-performance liquid chromatography (UHPLC) method for analysis by high-resolution mass spectrometry (MS). The use of UHPLC allowed for additional resolution needed to detect impurities and degradation products of interest. The secondary structure was probed using a combination of solution-state NMR, infrared, and circular dichroism spectroscopic methods. Solid-state NMR is used to detect amorphous API in a nondestructive manner directly within the coated sucrose sphere formulation. Fluorescence and Raman microscopy were used in conjunction with Raman mapping to show enteric coating integrity and observe the distribution of API beneath the enteric-coating on the sucrose spheres. The methods are combined in a multidisciplinary approach to characterize the quality of the enteric-coated peptide product.</description><identifier>ISSN: 0003-2700</identifier><identifier>EISSN: 1520-6882</identifier><identifier>DOI: 10.1021/ac203478r</identifier><identifier>PMID: 22497462</identifier><identifier>CODEN: ANCHAM</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Administration, Oral ; Amino Acid Sequence ; Analytical chemistry ; Chemistry ; Chromatographic methods and physical methods associated with chromatography ; Chromatography ; Chromatography, High Pressure Liquid ; Drug Compounding ; Exact sciences and technology ; Humans ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Molecular Sequence Data ; Molecular structure ; Other chromatographic methods ; Parathyroid Hormone - analysis ; Parathyroid Hormone - genetics ; Parathyroid Hormone - metabolism ; Peptides ; Peptides - analysis ; Pharmaceuticals ; Protein Structure, Secondary ; Recombinant Proteins - analysis ; Recombinant Proteins - genetics ; Recombinant Proteins - metabolism ; Spectrometric and optical methods ; Spectrum Analysis, Raman ; Sucrose - chemistry</subject><ispartof>Analytical chemistry (Washington), 2012-05, Vol.84 (10), p.4357-4372</ispartof><rights>Copyright © 2012 American Chemical Society</rights><rights>2015 INIST-CNRS</rights><rights>Copyright American Chemical Society May 15, 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a373t-d7eb84a929cf677366a3a84991457a5c4f1c131a600ec3e68422f0ebe542dcee3</citedby><cites>FETCH-LOGICAL-a373t-d7eb84a929cf677366a3a84991457a5c4f1c131a600ec3e68422f0ebe542dcee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/ac203478r$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/ac203478r$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25901114$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22497462$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kelley, Wayne P</creatorcontrib><creatorcontrib>Chen, Shujun</creatorcontrib><creatorcontrib>Floyd, Philip D</creatorcontrib><creatorcontrib>Hu, Ping</creatorcontrib><creatorcontrib>Kapsi, Shiva G</creatorcontrib><creatorcontrib>Kord, Alireza S</creatorcontrib><creatorcontrib>Sun, Mingjiang</creatorcontrib><creatorcontrib>Vogt, Frederick G</creatorcontrib><title>Analytical Characterization of an Orally-Delivered Peptide Pharmaceutical Product</title><title>Analytical chemistry (Washington)</title><addtitle>Anal. Chem</addtitle><description>The characterization of orally-delivered peptide pharmaceuticals presents several challenges to analytical methods in comparison to characterization of conventional small-molecule drugs. These challenges include the analysis and characterization of difficult-to-separate impurities, secondary structure, the amorphous solid-state form, and the integrity of enteric-coated drug delivery systems. This work presents the multidisciplinary analytical characterization of a parathyroid hormone (PTH) peptide active pharmaceutical ingredient (API) and an oral formulation of this API within enteric-coated sucrose spheres. The analysis of impurities and degradation products in API and formulated drug product was facilitated by the development of an ultrahigh-performance liquid chromatography (UHPLC) method for analysis by high-resolution mass spectrometry (MS). The use of UHPLC allowed for additional resolution needed to detect impurities and degradation products of interest. The secondary structure was probed using a combination of solution-state NMR, infrared, and circular dichroism spectroscopic methods. Solid-state NMR is used to detect amorphous API in a nondestructive manner directly within the coated sucrose sphere formulation. Fluorescence and Raman microscopy were used in conjunction with Raman mapping to show enteric coating integrity and observe the distribution of API beneath the enteric-coating on the sucrose spheres. The methods are combined in a multidisciplinary approach to characterize the quality of the enteric-coated peptide product.</description><subject>Administration, Oral</subject><subject>Amino Acid Sequence</subject><subject>Analytical chemistry</subject><subject>Chemistry</subject><subject>Chromatographic methods and physical methods associated with chromatography</subject><subject>Chromatography</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Drug Compounding</subject><subject>Exact sciences and technology</subject><subject>Humans</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Mass Spectrometry</subject><subject>Molecular Sequence Data</subject><subject>Molecular structure</subject><subject>Other chromatographic methods</subject><subject>Parathyroid Hormone - analysis</subject><subject>Parathyroid Hormone - genetics</subject><subject>Parathyroid Hormone - metabolism</subject><subject>Peptides</subject><subject>Peptides - analysis</subject><subject>Pharmaceuticals</subject><subject>Protein Structure, Secondary</subject><subject>Recombinant Proteins - analysis</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - metabolism</subject><subject>Spectrometric and optical methods</subject><subject>Spectrum Analysis, Raman</subject><subject>Sucrose - chemistry</subject><issn>0003-2700</issn><issn>1520-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0VtLwzAUB_AgipvTB7-AFETQh2puTZrHMa8w2AR9LmfpKXZ07UxaYX56o5tT9pSXX87lfwg5ZfSaUc5uwHIqpE7dHumzhNNYpSnfJ31KqYi5prRHjryfU8oYZeqQ9DiXRkvF--R5WEO1aksLVTR6Awe2RVd-Qls2ddQUEdTRxEFVreJbrMoPdJhHU1y2ZY7RNPgFWOzW36euyTvbHpODAiqPJ5t3QF7v715Gj_F48vA0Go5jEFq0ca5xlkow3NhCaS2UAgGpNIbJRENiZcEsEwwUpWgFqlRyXlCcYSJ5bhHFgFyu6y5d896hb7NF6S1WFdTYdD4LqwrDVcpNoOc7dN50Liz-oxLFqeE6qKu1sq7x3mGRLV25ALcKKPvOOdvmHOzZpmI3W2C-lb_BBnCxAeBDOIWD2pb-zyUmHIPJPwfW_59qt-EXw9mPvA</recordid><startdate>20120515</startdate><enddate>20120515</enddate><creator>Kelley, Wayne P</creator><creator>Chen, Shujun</creator><creator>Floyd, Philip D</creator><creator>Hu, Ping</creator><creator>Kapsi, Shiva G</creator><creator>Kord, Alireza S</creator><creator>Sun, Mingjiang</creator><creator>Vogt, Frederick G</creator><general>American Chemical Society</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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7U5</scope><scope>7U7</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20120515</creationdate><title>Analytical Characterization of an Orally-Delivered Peptide Pharmaceutical Product</title><author>Kelley, Wayne P ; Chen, Shujun ; Floyd, Philip D ; Hu, Ping ; Kapsi, Shiva G ; Kord, Alireza S ; Sun, Mingjiang ; Vogt, Frederick G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a373t-d7eb84a929cf677366a3a84991457a5c4f1c131a600ec3e68422f0ebe542dcee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Administration, Oral</topic><topic>Amino Acid Sequence</topic><topic>Analytical chemistry</topic><topic>Chemistry</topic><topic>Chromatographic methods and physical methods associated with chromatography</topic><topic>Chromatography</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Drug Compounding</topic><topic>Exact sciences and technology</topic><topic>Humans</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Mass Spectrometry</topic><topic>Molecular Sequence Data</topic><topic>Molecular structure</topic><topic>Other chromatographic methods</topic><topic>Parathyroid Hormone - analysis</topic><topic>Parathyroid Hormone - genetics</topic><topic>Parathyroid Hormone - metabolism</topic><topic>Peptides</topic><topic>Peptides - analysis</topic><topic>Pharmaceuticals</topic><topic>Protein Structure, Secondary</topic><topic>Recombinant Proteins - analysis</topic><topic>Recombinant Proteins - genetics</topic><topic>Recombinant Proteins - metabolism</topic><topic>Spectrometric and optical methods</topic><topic>Spectrum Analysis, Raman</topic><topic>Sucrose - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kelley, Wayne P</creatorcontrib><creatorcontrib>Chen, Shujun</creatorcontrib><creatorcontrib>Floyd, Philip D</creatorcontrib><creatorcontrib>Hu, Ping</creatorcontrib><creatorcontrib>Kapsi, Shiva G</creatorcontrib><creatorcontrib>Kord, Alireza S</creatorcontrib><creatorcontrib>Sun, Mingjiang</creatorcontrib><creatorcontrib>Vogt, Frederick G</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>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Analytical chemistry (Washington)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kelley, Wayne P</au><au>Chen, Shujun</au><au>Floyd, Philip D</au><au>Hu, Ping</au><au>Kapsi, Shiva G</au><au>Kord, Alireza S</au><au>Sun, Mingjiang</au><au>Vogt, Frederick G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analytical Characterization of an Orally-Delivered Peptide Pharmaceutical Product</atitle><jtitle>Analytical chemistry (Washington)</jtitle><addtitle>Anal. Chem</addtitle><date>2012-05-15</date><risdate>2012</risdate><volume>84</volume><issue>10</issue><spage>4357</spage><epage>4372</epage><pages>4357-4372</pages><issn>0003-2700</issn><eissn>1520-6882</eissn><coden>ANCHAM</coden><abstract>The characterization of orally-delivered peptide pharmaceuticals presents several challenges to analytical methods in comparison to characterization of conventional small-molecule drugs. These challenges include the analysis and characterization of difficult-to-separate impurities, secondary structure, the amorphous solid-state form, and the integrity of enteric-coated drug delivery systems. This work presents the multidisciplinary analytical characterization of a parathyroid hormone (PTH) peptide active pharmaceutical ingredient (API) and an oral formulation of this API within enteric-coated sucrose spheres. The analysis of impurities and degradation products in API and formulated drug product was facilitated by the development of an ultrahigh-performance liquid chromatography (UHPLC) method for analysis by high-resolution mass spectrometry (MS). The use of UHPLC allowed for additional resolution needed to detect impurities and degradation products of interest. The secondary structure was probed using a combination of solution-state NMR, infrared, and circular dichroism spectroscopic methods. Solid-state NMR is used to detect amorphous API in a nondestructive manner directly within the coated sucrose sphere formulation. Fluorescence and Raman microscopy were used in conjunction with Raman mapping to show enteric coating integrity and observe the distribution of API beneath the enteric-coating on the sucrose spheres. The methods are combined in a multidisciplinary approach to characterize the quality of the enteric-coated peptide product.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>22497462</pmid><doi>10.1021/ac203478r</doi><tpages>16</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0003-2700 |
| ispartof | Analytical chemistry (Washington), 2012-05, Vol.84 (10), p.4357-4372 |
| issn | 0003-2700 1520-6882 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1013926829 |
| source | MEDLINE; American Chemical Society Journals |
| subjects | Administration, Oral Amino Acid Sequence Analytical chemistry Chemistry Chromatographic methods and physical methods associated with chromatography Chromatography Chromatography, High Pressure Liquid Drug Compounding Exact sciences and technology Humans Magnetic Resonance Spectroscopy Mass Spectrometry Molecular Sequence Data Molecular structure Other chromatographic methods Parathyroid Hormone - analysis Parathyroid Hormone - genetics Parathyroid Hormone - metabolism Peptides Peptides - analysis Pharmaceuticals Protein Structure, Secondary Recombinant Proteins - analysis Recombinant Proteins - genetics Recombinant Proteins - metabolism Spectrometric and optical methods Spectrum Analysis, Raman Sucrose - chemistry |
| title | Analytical Characterization of an Orally-Delivered Peptide Pharmaceutical Product |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T12%3A56%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Analytical%20Characterization%20of%20an%20Orally-Delivered%20Peptide%20Pharmaceutical%20Product&rft.jtitle=Analytical%20chemistry%20(Washington)&rft.au=Kelley,%20Wayne%20P&rft.date=2012-05-15&rft.volume=84&rft.issue=10&rft.spage=4357&rft.epage=4372&rft.pages=4357-4372&rft.issn=0003-2700&rft.eissn=1520-6882&rft.coden=ANCHAM&rft_id=info:doi/10.1021/ac203478r&rft_dat=%3Cproquest_cross%3E1013926829%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1015620927&rft_id=info:pmid/22497462&rfr_iscdi=true |