Drug substance manufacture process control: application of flow injection analysis and HPLC for monitoring an enantiospecific synthesis
Effective process control can only be achieved through an understanding of the operating issues of the reaction. The development and use of effective and rugged analytical methods is necessary to monitor these parameters. The intent of this paper is to present some key analytical issues encountered...
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| Veröffentlicht in: | Journal of pharmaceutical and biomedical analysis 1996-10, Vol.15 (1), p.111-121 |
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| container_end_page | 121 |
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| container_title | Journal of pharmaceutical and biomedical analysis |
| container_volume | 15 |
| creator | Chong, K. Loughlin, T. Moeder, C. Perpall, H.J. Thompson, R. Grinberg, N. Smith, G.B. Bhupathy, M. Bicker, G. |
| description | Effective process control can only be achieved through an understanding of the operating issues of the reaction. The development and use of effective and rugged analytical methods is necessary to monitor these parameters. The intent of this paper is to present some key analytical issues encountered in the synthesis of MK-0679, an LTD
4 antagonist. In a key step of the compound's synthesis, a prochiral diester intermediate undergoes an enantioselective enzymatic hydrolysis (in the presence of Triton X-100) leading to the (
S)-ester acid. Subsequent processing transforms the ester acid into the final product. The residual amount of the detergent in the final product, the rapid determination of the enzymatic activity and the optical purity of the final product emerged as key issues in the control of the reaction. As a solution, two techniques were utilized and are presented: flow injection analysis and HPLC. |
| doi_str_mv | 10.1016/0731-7085(96)01810-9 |
| format | Article |
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4 antagonist. In a key step of the compound's synthesis, a prochiral diester intermediate undergoes an enantioselective enzymatic hydrolysis (in the presence of Triton X-100) leading to the (
S)-ester acid. Subsequent processing transforms the ester acid into the final product. The residual amount of the detergent in the final product, the rapid determination of the enzymatic activity and the optical purity of the final product emerged as key issues in the control of the reaction. As a solution, two techniques were utilized and are presented: flow injection analysis and HPLC.</description><identifier>ISSN: 0731-7085</identifier><identifier>EISSN: 1873-264X</identifier><identifier>DOI: 10.1016/0731-7085(96)01810-9</identifier><identifier>PMID: 8895082</identifier><identifier>CODEN: JPBADA</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Biological and medical sciences ; Chromatography, High Pressure Liquid - methods ; Diastereomers ; Enantiomeric separation ; Enzyme activity ; Flow injection ; Flow Injection Analysis - methods ; General pharmacology ; Leukotriene D4 - antagonists & inhibitors ; Medical sciences ; Octoxynol - analysis ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Propionates - analysis ; Propionates - chemical synthesis ; Quinolines - analysis ; Quinolines - chemical synthesis ; Stereoisomerism ; Technology, Pharmaceutical</subject><ispartof>Journal of pharmaceutical and biomedical analysis, 1996-10, Vol.15 (1), p.111-121</ispartof><rights>1996</rights><rights>1996 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-6f0a2260a899a243062fe37b390c114efce863ec40f8cc3683b345313222eef83</citedby><cites>FETCH-LOGICAL-c386t-6f0a2260a899a243062fe37b390c114efce863ec40f8cc3683b345313222eef83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0731-7085(96)01810-9$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3225157$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8895082$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chong, K.</creatorcontrib><creatorcontrib>Loughlin, T.</creatorcontrib><creatorcontrib>Moeder, C.</creatorcontrib><creatorcontrib>Perpall, H.J.</creatorcontrib><creatorcontrib>Thompson, R.</creatorcontrib><creatorcontrib>Grinberg, N.</creatorcontrib><creatorcontrib>Smith, G.B.</creatorcontrib><creatorcontrib>Bhupathy, M.</creatorcontrib><creatorcontrib>Bicker, G.</creatorcontrib><title>Drug substance manufacture process control: application of flow injection analysis and HPLC for monitoring an enantiospecific synthesis</title><title>Journal of pharmaceutical and biomedical analysis</title><addtitle>J Pharm Biomed Anal</addtitle><description>Effective process control can only be achieved through an understanding of the operating issues of the reaction. The development and use of effective and rugged analytical methods is necessary to monitor these parameters. The intent of this paper is to present some key analytical issues encountered in the synthesis of MK-0679, an LTD
4 antagonist. In a key step of the compound's synthesis, a prochiral diester intermediate undergoes an enantioselective enzymatic hydrolysis (in the presence of Triton X-100) leading to the (
S)-ester acid. Subsequent processing transforms the ester acid into the final product. The residual amount of the detergent in the final product, the rapid determination of the enzymatic activity and the optical purity of the final product emerged as key issues in the control of the reaction. As a solution, two techniques were utilized and are presented: flow injection analysis and HPLC.</description><subject>Biological and medical sciences</subject><subject>Chromatography, High Pressure Liquid - methods</subject><subject>Diastereomers</subject><subject>Enantiomeric separation</subject><subject>Enzyme activity</subject><subject>Flow injection</subject><subject>Flow Injection Analysis - methods</subject><subject>General pharmacology</subject><subject>Leukotriene D4 - antagonists & inhibitors</subject><subject>Medical sciences</subject><subject>Octoxynol - analysis</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Propionates - analysis</subject><subject>Propionates - chemical synthesis</subject><subject>Quinolines - analysis</subject><subject>Quinolines - chemical synthesis</subject><subject>Stereoisomerism</subject><subject>Technology, Pharmaceutical</subject><issn>0731-7085</issn><issn>1873-264X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU2vEyEUhonRXGv1H2jCwhhdjPIxw4ALE1M_rkkTXWjijlB6uHIzAyNnRtNf4N-W2qZLV8DheU8OD4Q85uwlZ1y9Yr3kTc9099yoF4xrzhpzh6y47mUjVPv9LlldkPvkAeItY6zjpr0iV1qbjmmxIn_eleWG4rLD2SUPdHRpCc7PSwE6lewBkfqc5pKH19RN0xC9m2NONAcahvybxnQL_l_FJTccMGLd7On1l-2GhlzomFOcc4npptYpJJcqjBP4GKKneEjzD6ihh-RecAPCo_O6Jt8-vP-6uW62nz9-2rzdNl5qNTcqMCeEYk4b40QrmRIBZL-ThnnOWwgetJLgWxa091JpuZNtJ7kUQgAELdfk2alvfdzPBXC2Y0QPw-AS5AVtr1vdiRpZk_YE-pIRCwQ7lTi6crCc2aN_e5Rrj3KtqYejf2tq7Mm5_7IbYX8JnYXX-6fne4feDaFU6xEvWJ2z411fsTcnDKqLXxGKRR-hftA-lqrb7nP8_xx_ARxLo8Q</recordid><startdate>19961001</startdate><enddate>19961001</enddate><creator>Chong, K.</creator><creator>Loughlin, T.</creator><creator>Moeder, C.</creator><creator>Perpall, H.J.</creator><creator>Thompson, R.</creator><creator>Grinberg, N.</creator><creator>Smith, G.B.</creator><creator>Bhupathy, M.</creator><creator>Bicker, G.</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>19961001</creationdate><title>Drug substance manufacture process control: application of flow injection analysis and HPLC for monitoring an enantiospecific synthesis</title><author>Chong, K. ; Loughlin, T. ; Moeder, C. ; Perpall, H.J. ; Thompson, R. ; Grinberg, N. ; Smith, G.B. ; Bhupathy, M. ; Bicker, G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-6f0a2260a899a243062fe37b390c114efce863ec40f8cc3683b345313222eef83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Biological and medical sciences</topic><topic>Chromatography, High Pressure Liquid - methods</topic><topic>Diastereomers</topic><topic>Enantiomeric separation</topic><topic>Enzyme activity</topic><topic>Flow injection</topic><topic>Flow Injection Analysis - methods</topic><topic>General pharmacology</topic><topic>Leukotriene D4 - antagonists & inhibitors</topic><topic>Medical sciences</topic><topic>Octoxynol - analysis</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Propionates - analysis</topic><topic>Propionates - chemical synthesis</topic><topic>Quinolines - analysis</topic><topic>Quinolines - chemical synthesis</topic><topic>Stereoisomerism</topic><topic>Technology, Pharmaceutical</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chong, K.</creatorcontrib><creatorcontrib>Loughlin, T.</creatorcontrib><creatorcontrib>Moeder, C.</creatorcontrib><creatorcontrib>Perpall, H.J.</creatorcontrib><creatorcontrib>Thompson, R.</creatorcontrib><creatorcontrib>Grinberg, N.</creatorcontrib><creatorcontrib>Smith, G.B.</creatorcontrib><creatorcontrib>Bhupathy, M.</creatorcontrib><creatorcontrib>Bicker, 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>MEDLINE - Academic</collection><jtitle>Journal of pharmaceutical and biomedical analysis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chong, K.</au><au>Loughlin, T.</au><au>Moeder, C.</au><au>Perpall, H.J.</au><au>Thompson, R.</au><au>Grinberg, N.</au><au>Smith, G.B.</au><au>Bhupathy, M.</au><au>Bicker, G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Drug substance manufacture process control: application of flow injection analysis and HPLC for monitoring an enantiospecific synthesis</atitle><jtitle>Journal of pharmaceutical and biomedical analysis</jtitle><addtitle>J Pharm Biomed Anal</addtitle><date>1996-10-01</date><risdate>1996</risdate><volume>15</volume><issue>1</issue><spage>111</spage><epage>121</epage><pages>111-121</pages><issn>0731-7085</issn><eissn>1873-264X</eissn><coden>JPBADA</coden><abstract>Effective process control can only be achieved through an understanding of the operating issues of the reaction. The development and use of effective and rugged analytical methods is necessary to monitor these parameters. The intent of this paper is to present some key analytical issues encountered in the synthesis of MK-0679, an LTD
4 antagonist. In a key step of the compound's synthesis, a prochiral diester intermediate undergoes an enantioselective enzymatic hydrolysis (in the presence of Triton X-100) leading to the (
S)-ester acid. Subsequent processing transforms the ester acid into the final product. The residual amount of the detergent in the final product, the rapid determination of the enzymatic activity and the optical purity of the final product emerged as key issues in the control of the reaction. As a solution, two techniques were utilized and are presented: flow injection analysis and HPLC.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>8895082</pmid><doi>10.1016/0731-7085(96)01810-9</doi><tpages>11</tpages></addata></record> |
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| ispartof | Journal of pharmaceutical and biomedical analysis, 1996-10, Vol.15 (1), p.111-121 |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Biological and medical sciences Chromatography, High Pressure Liquid - methods Diastereomers Enantiomeric separation Enzyme activity Flow injection Flow Injection Analysis - methods General pharmacology Leukotriene D4 - antagonists & inhibitors Medical sciences Octoxynol - analysis Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Propionates - analysis Propionates - chemical synthesis Quinolines - analysis Quinolines - chemical synthesis Stereoisomerism Technology, Pharmaceutical |
| title | Drug substance manufacture process control: application of flow injection analysis and HPLC for monitoring an enantiospecific synthesis |
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