A New Strategy to Stabilize Oxytocin in Aqueous Solutions: I. The Effects of Divalent Metal Ions and Citrate Buffer
In the current study, the effect of metal ions in combination with buffers (citrate, acetate, pH 4.5) on the stability of aqueous solutions of oxytocin was investigated. Both monovalent metal ions (Na + and K + ) and divalent metal ions (Ca 2+ , Mg 2+ , and Zn 2+ ) were tested all as chloride salts....
Gespeichert in:
| Veröffentlicht in: | The AAPS journal 2011-06, Vol.13 (2), p.284-290 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 290 |
|---|---|
| container_issue | 2 |
| container_start_page | 284 |
| container_title | The AAPS journal |
| container_volume | 13 |
| creator | Avanti, Christina Amorij, Jean-Pierre Setyaningsih, Dewi Hawe, Andrea Jiskoot, Wim Visser, Jan Kedrov, Alexej Driessen, Arnold J. M. Hinrichs, Wouter L. J. Frijlink, Henderik W. |
| description | In the current study, the effect of metal ions in combination with buffers (citrate, acetate, pH 4.5) on the stability of aqueous solutions of oxytocin was investigated. Both monovalent metal ions (Na
+
and K
+
) and divalent metal ions (Ca
2+
, Mg
2+
, and Zn
2+
) were tested all as chloride salts. The effect of combinations of buffers and metal ions on the stability of aqueous oxytocin solutions was determined by RP-HPLC and HP-SEC after 4 weeks of storage at either 4°C or 55°C. Addition of sodium or potassium ions to acetate- or citrate-buffered solutions did not increase stability, nor did the addition of divalent metal ions to acetate buffer. However, the stability of aqueous oxytocin in aqueous formulations was improved in the presence of 5 and 10 mM citrate buffer in combination with at least 2 mM CaCl
2
, MgCl
2
, or ZnCl
2
and depended on the divalent metal ion concentration. Isothermal titration calorimetric measurements were predictive for the stabilization effects observed during the stability study. Formulations in citrate buffer that had an improved stability displayed a strong interaction between oxytocin and Ca
2+
, Mg
2+
, or Zn
2+
, while formulations in acetate buffer did not. In conclusion, our study shows that divalent metal ions in combination with citrate buffer strongly improved the stability of oxytocin in aqueous solutions. |
| doi_str_mv | 10.1208/s12248-011-9268-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3085697</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>864785127</sourcerecordid><originalsourceid>FETCH-LOGICAL-c441t-1b60c5222c4638f95f698e2f50b1d65e651ff990fbeb6d9b81d3c2a5dc0e40c03</originalsourceid><addsrcrecordid>eNp9kU1v1DAQhi0Eoh_wA7gg3zil9Ti243BAWpZSVmrpoeVsOY69dZWNi-0Utr8ehy1VuVQaaUaaZ16P50XoHZAjoEQeJ6CUyYoAVC0VsmpeoH3gnFQNA_HySb2HDlK6IaSmNcBrtEeBMdmwZh-lBf5uf-HLHHW26y3OodS684O_t_ji9zYH40dcYvFzsmFK-DIMU_ZhTB_x6ghfXVt84pw1OeHg8Bd_pwc7Znxusx7wqmBYjz1e-r_6-PNU2PgGvXJ6SPbtQz5EP76eXC2_VWcXp6vl4qwyjEGuoBPEcEqpYaKWruVOtNJSx0kHveBWcHCubYnrbCf6tpPQ14Zq3htiGTGkPkSfdrq3U7exvSmLRT2o2-g3Om5V0F793xn9tVqHO1UTyUXbFIEPDwIxlO-nrDY-GTsMepxvoaRgjeRAZxJ2pIkhpWjd4ytA1OyV2nmlildq9krNM--frvc48c-cAtAdkEprXNuobsIUx3KyZ1T_AJ3qoGw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>864785127</pqid></control><display><type>article</type><title>A New Strategy to Stabilize Oxytocin in Aqueous Solutions: I. The Effects of Divalent Metal Ions and Citrate Buffer</title><source>MEDLINE</source><source>PubMed Central</source><source>SpringerLink Journals - AutoHoldings</source><creator>Avanti, Christina ; Amorij, Jean-Pierre ; Setyaningsih, Dewi ; Hawe, Andrea ; Jiskoot, Wim ; Visser, Jan ; Kedrov, Alexej ; Driessen, Arnold J. M. ; Hinrichs, Wouter L. J. ; Frijlink, Henderik W.</creator><creatorcontrib>Avanti, Christina ; Amorij, Jean-Pierre ; Setyaningsih, Dewi ; Hawe, Andrea ; Jiskoot, Wim ; Visser, Jan ; Kedrov, Alexej ; Driessen, Arnold J. M. ; Hinrichs, Wouter L. J. ; Frijlink, Henderik W.</creatorcontrib><description>In the current study, the effect of metal ions in combination with buffers (citrate, acetate, pH 4.5) on the stability of aqueous solutions of oxytocin was investigated. Both monovalent metal ions (Na
+
and K
+
) and divalent metal ions (Ca
2+
, Mg
2+
, and Zn
2+
) were tested all as chloride salts. The effect of combinations of buffers and metal ions on the stability of aqueous oxytocin solutions was determined by RP-HPLC and HP-SEC after 4 weeks of storage at either 4°C or 55°C. Addition of sodium or potassium ions to acetate- or citrate-buffered solutions did not increase stability, nor did the addition of divalent metal ions to acetate buffer. However, the stability of aqueous oxytocin in aqueous formulations was improved in the presence of 5 and 10 mM citrate buffer in combination with at least 2 mM CaCl
2
, MgCl
2
, or ZnCl
2
and depended on the divalent metal ion concentration. Isothermal titration calorimetric measurements were predictive for the stabilization effects observed during the stability study. Formulations in citrate buffer that had an improved stability displayed a strong interaction between oxytocin and Ca
2+
, Mg
2+
, or Zn
2+
, while formulations in acetate buffer did not. In conclusion, our study shows that divalent metal ions in combination with citrate buffer strongly improved the stability of oxytocin in aqueous solutions.</description><identifier>ISSN: 1550-7416</identifier><identifier>EISSN: 1550-7416</identifier><identifier>DOI: 10.1208/s12248-011-9268-7</identifier><identifier>PMID: 21448747</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; Buffers ; Chromatography, High Pressure Liquid - methods ; Citrates - chemistry ; Drug Stability ; Drug Storage ; Metals - chemistry ; Oxytocics - administration & dosage ; Oxytocics - chemistry ; Oxytocin - administration & dosage ; Oxytocin - chemistry ; Pharmaceutical Solutions ; Pharmacology/Toxicology ; Pharmacy ; Research Article ; Temperature</subject><ispartof>The AAPS journal, 2011-06, Vol.13 (2), p.284-290</ispartof><rights>The Author(s) 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-1b60c5222c4638f95f698e2f50b1d65e651ff990fbeb6d9b81d3c2a5dc0e40c03</citedby><cites>FETCH-LOGICAL-c441t-1b60c5222c4638f95f698e2f50b1d65e651ff990fbeb6d9b81d3c2a5dc0e40c03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085697/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085697/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21448747$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Avanti, Christina</creatorcontrib><creatorcontrib>Amorij, Jean-Pierre</creatorcontrib><creatorcontrib>Setyaningsih, Dewi</creatorcontrib><creatorcontrib>Hawe, Andrea</creatorcontrib><creatorcontrib>Jiskoot, Wim</creatorcontrib><creatorcontrib>Visser, Jan</creatorcontrib><creatorcontrib>Kedrov, Alexej</creatorcontrib><creatorcontrib>Driessen, Arnold J. M.</creatorcontrib><creatorcontrib>Hinrichs, Wouter L. J.</creatorcontrib><creatorcontrib>Frijlink, Henderik W.</creatorcontrib><title>A New Strategy to Stabilize Oxytocin in Aqueous Solutions: I. The Effects of Divalent Metal Ions and Citrate Buffer</title><title>The AAPS journal</title><addtitle>AAPS J</addtitle><addtitle>AAPS J</addtitle><description>In the current study, the effect of metal ions in combination with buffers (citrate, acetate, pH 4.5) on the stability of aqueous solutions of oxytocin was investigated. Both monovalent metal ions (Na
+
and K
+
) and divalent metal ions (Ca
2+
, Mg
2+
, and Zn
2+
) were tested all as chloride salts. The effect of combinations of buffers and metal ions on the stability of aqueous oxytocin solutions was determined by RP-HPLC and HP-SEC after 4 weeks of storage at either 4°C or 55°C. Addition of sodium or potassium ions to acetate- or citrate-buffered solutions did not increase stability, nor did the addition of divalent metal ions to acetate buffer. However, the stability of aqueous oxytocin in aqueous formulations was improved in the presence of 5 and 10 mM citrate buffer in combination with at least 2 mM CaCl
2
, MgCl
2
, or ZnCl
2
and depended on the divalent metal ion concentration. Isothermal titration calorimetric measurements were predictive for the stabilization effects observed during the stability study. Formulations in citrate buffer that had an improved stability displayed a strong interaction between oxytocin and Ca
2+
, Mg
2+
, or Zn
2+
, while formulations in acetate buffer did not. In conclusion, our study shows that divalent metal ions in combination with citrate buffer strongly improved the stability of oxytocin in aqueous solutions.</description><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Buffers</subject><subject>Chromatography, High Pressure Liquid - methods</subject><subject>Citrates - chemistry</subject><subject>Drug Stability</subject><subject>Drug Storage</subject><subject>Metals - chemistry</subject><subject>Oxytocics - administration & dosage</subject><subject>Oxytocics - chemistry</subject><subject>Oxytocin - administration & dosage</subject><subject>Oxytocin - chemistry</subject><subject>Pharmaceutical Solutions</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><subject>Research Article</subject><subject>Temperature</subject><issn>1550-7416</issn><issn>1550-7416</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi0Eoh_wA7gg3zil9Ti243BAWpZSVmrpoeVsOY69dZWNi-0Utr8ehy1VuVQaaUaaZ16P50XoHZAjoEQeJ6CUyYoAVC0VsmpeoH3gnFQNA_HySb2HDlK6IaSmNcBrtEeBMdmwZh-lBf5uf-HLHHW26y3OodS684O_t_ji9zYH40dcYvFzsmFK-DIMU_ZhTB_x6ghfXVt84pw1OeHg8Bd_pwc7Znxusx7wqmBYjz1e-r_6-PNU2PgGvXJ6SPbtQz5EP76eXC2_VWcXp6vl4qwyjEGuoBPEcEqpYaKWruVOtNJSx0kHveBWcHCubYnrbCf6tpPQ14Zq3htiGTGkPkSfdrq3U7exvSmLRT2o2-g3Om5V0F793xn9tVqHO1UTyUXbFIEPDwIxlO-nrDY-GTsMepxvoaRgjeRAZxJ2pIkhpWjd4ytA1OyV2nmlildq9krNM--frvc48c-cAtAdkEprXNuobsIUx3KyZ1T_AJ3qoGw</recordid><startdate>20110601</startdate><enddate>20110601</enddate><creator>Avanti, Christina</creator><creator>Amorij, Jean-Pierre</creator><creator>Setyaningsih, Dewi</creator><creator>Hawe, Andrea</creator><creator>Jiskoot, Wim</creator><creator>Visser, Jan</creator><creator>Kedrov, Alexej</creator><creator>Driessen, Arnold J. M.</creator><creator>Hinrichs, Wouter L. J.</creator><creator>Frijlink, Henderik W.</creator><general>Springer US</general><scope>C6C</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><scope>5PM</scope></search><sort><creationdate>20110601</creationdate><title>A New Strategy to Stabilize Oxytocin in Aqueous Solutions: I. The Effects of Divalent Metal Ions and Citrate Buffer</title><author>Avanti, Christina ; Amorij, Jean-Pierre ; Setyaningsih, Dewi ; Hawe, Andrea ; Jiskoot, Wim ; Visser, Jan ; Kedrov, Alexej ; Driessen, Arnold J. M. ; Hinrichs, Wouter L. J. ; Frijlink, Henderik W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-1b60c5222c4638f95f698e2f50b1d65e651ff990fbeb6d9b81d3c2a5dc0e40c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Buffers</topic><topic>Chromatography, High Pressure Liquid - methods</topic><topic>Citrates - chemistry</topic><topic>Drug Stability</topic><topic>Drug Storage</topic><topic>Metals - chemistry</topic><topic>Oxytocics - administration & dosage</topic><topic>Oxytocics - chemistry</topic><topic>Oxytocin - administration & dosage</topic><topic>Oxytocin - chemistry</topic><topic>Pharmaceutical Solutions</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>Research Article</topic><topic>Temperature</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Avanti, Christina</creatorcontrib><creatorcontrib>Amorij, Jean-Pierre</creatorcontrib><creatorcontrib>Setyaningsih, Dewi</creatorcontrib><creatorcontrib>Hawe, Andrea</creatorcontrib><creatorcontrib>Jiskoot, Wim</creatorcontrib><creatorcontrib>Visser, Jan</creatorcontrib><creatorcontrib>Kedrov, Alexej</creatorcontrib><creatorcontrib>Driessen, Arnold J. M.</creatorcontrib><creatorcontrib>Hinrichs, Wouter L. J.</creatorcontrib><creatorcontrib>Frijlink, Henderik W.</creatorcontrib><collection>Springer Nature OA/Free Journals</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>The AAPS journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Avanti, Christina</au><au>Amorij, Jean-Pierre</au><au>Setyaningsih, Dewi</au><au>Hawe, Andrea</au><au>Jiskoot, Wim</au><au>Visser, Jan</au><au>Kedrov, Alexej</au><au>Driessen, Arnold J. M.</au><au>Hinrichs, Wouter L. J.</au><au>Frijlink, Henderik W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A New Strategy to Stabilize Oxytocin in Aqueous Solutions: I. The Effects of Divalent Metal Ions and Citrate Buffer</atitle><jtitle>The AAPS journal</jtitle><stitle>AAPS J</stitle><addtitle>AAPS J</addtitle><date>2011-06-01</date><risdate>2011</risdate><volume>13</volume><issue>2</issue><spage>284</spage><epage>290</epage><pages>284-290</pages><issn>1550-7416</issn><eissn>1550-7416</eissn><abstract>In the current study, the effect of metal ions in combination with buffers (citrate, acetate, pH 4.5) on the stability of aqueous solutions of oxytocin was investigated. Both monovalent metal ions (Na
+
and K
+
) and divalent metal ions (Ca
2+
, Mg
2+
, and Zn
2+
) were tested all as chloride salts. The effect of combinations of buffers and metal ions on the stability of aqueous oxytocin solutions was determined by RP-HPLC and HP-SEC after 4 weeks of storage at either 4°C or 55°C. Addition of sodium or potassium ions to acetate- or citrate-buffered solutions did not increase stability, nor did the addition of divalent metal ions to acetate buffer. However, the stability of aqueous oxytocin in aqueous formulations was improved in the presence of 5 and 10 mM citrate buffer in combination with at least 2 mM CaCl
2
, MgCl
2
, or ZnCl
2
and depended on the divalent metal ion concentration. Isothermal titration calorimetric measurements were predictive for the stabilization effects observed during the stability study. Formulations in citrate buffer that had an improved stability displayed a strong interaction between oxytocin and Ca
2+
, Mg
2+
, or Zn
2+
, while formulations in acetate buffer did not. In conclusion, our study shows that divalent metal ions in combination with citrate buffer strongly improved the stability of oxytocin in aqueous solutions.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>21448747</pmid><doi>10.1208/s12248-011-9268-7</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1550-7416 |
| ispartof | The AAPS journal, 2011-06, Vol.13 (2), p.284-290 |
| issn | 1550-7416 1550-7416 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3085697 |
| source | MEDLINE; PubMed Central; SpringerLink Journals - AutoHoldings |
| subjects | Biochemistry Biomedical and Life Sciences Biomedicine Biotechnology Buffers Chromatography, High Pressure Liquid - methods Citrates - chemistry Drug Stability Drug Storage Metals - chemistry Oxytocics - administration & dosage Oxytocics - chemistry Oxytocin - administration & dosage Oxytocin - chemistry Pharmaceutical Solutions Pharmacology/Toxicology Pharmacy Research Article Temperature |
| title | A New Strategy to Stabilize Oxytocin in Aqueous Solutions: I. The Effects of Divalent Metal Ions and Citrate Buffer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T06%3A14%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20New%20Strategy%20to%20Stabilize%20Oxytocin%20in%20Aqueous%20Solutions:%20I.%20The%20Effects%20of%20Divalent%20Metal%20Ions%20and%20Citrate%20Buffer&rft.jtitle=The%20AAPS%20journal&rft.au=Avanti,%20Christina&rft.date=2011-06-01&rft.volume=13&rft.issue=2&rft.spage=284&rft.epage=290&rft.pages=284-290&rft.issn=1550-7416&rft.eissn=1550-7416&rft_id=info:doi/10.1208/s12248-011-9268-7&rft_dat=%3Cproquest_pubme%3E864785127%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=864785127&rft_id=info:pmid/21448747&rfr_iscdi=true |