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A HPLC method for simultaneous quantification of chlorhexidine and thymol using Box-Behnken design for robustness of the method assessment
The antimicrobial chlorhexidine is considered the gold standard in dentistry. Thymol is a phenol found in the essential oils of various plant species and also stands out for its antimicrobial potential. Synergistic effects can be promoted by applying these two active pharmaceutical ingredients toget...
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Published in: | Journal of liquid chromatography & related technologies 2023-09, Vol.46 (6-10), p.168-179 |
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container_title | Journal of liquid chromatography & related technologies |
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description | The antimicrobial chlorhexidine is considered the gold standard in dentistry. Thymol is a phenol found in the essential oils of various plant species and also stands out for its antimicrobial potential. Synergistic effects can be promoted by applying these two active pharmaceutical ingredients together in technological products, for example in controlled release microparticles. The objective of this work was to develop and validate an analytical methodology applying a Box-Behnken experimental design and using High Performance Liquid Chromatography capable of quantifying chlorhexidine and thymol simultaneously in a matrix including pharmaceutical excipients. After optimization, the mobile phase consisted of methanol and 0.03 M monobasic sodium phosphate buffer (60:40), with 0.4% triethylamine and octylsilane as the applied stationary phase. The method proved selective, even in the presence of chlorhexidine and thymol degradation products. For chlorhexidine, the method was linear from 4.8 to 19.2 µg/mL, and for thymol from 8.0 to 32.0 µg/mL. Accuracy was close to 100%, and the precision assessment yielded coefficient variation values of |
doi_str_mv | 10.1080/10826076.2023.2227792 |
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Thymol is a phenol found in the essential oils of various plant species and also stands out for its antimicrobial potential. Synergistic effects can be promoted by applying these two active pharmaceutical ingredients together in technological products, for example in controlled release microparticles. The objective of this work was to develop and validate an analytical methodology applying a Box-Behnken experimental design and using High Performance Liquid Chromatography capable of quantifying chlorhexidine and thymol simultaneously in a matrix including pharmaceutical excipients. After optimization, the mobile phase consisted of methanol and 0.03 M monobasic sodium phosphate buffer (60:40), with 0.4% triethylamine and octylsilane as the applied stationary phase. The method proved selective, even in the presence of chlorhexidine and thymol degradation products. For chlorhexidine, the method was linear from 4.8 to 19.2 µg/mL, and for thymol from 8.0 to 32.0 µg/mL. Accuracy was close to 100%, and the precision assessment yielded coefficient variation values of <5%. Being based on the Box-Behnken design, the method was robust and therefore validated for assisting in quality control processes involving these active pharmaceutical ingredients.</description><identifier>ISSN: 1082-6076</identifier><identifier>EISSN: 1520-572X</identifier><identifier>DOI: 10.1080/10826076.2023.2227792</identifier><language>eng</language><publisher>Abingdon: Taylor & Francis</publisher><subject>Active control ; Antiinfectives and antibacterials ; Box-Behnken ; Chlorhexidine ; Coefficient of variation ; Controlled release ; Degradation products ; Dentistry ; Design of experiments ; Essential oils ; Experimental design ; High performance liquid chromatography ; HPLC ; Ingredients ; Ions ; Liquid chromatography ; Mathematical analysis ; Microparticles ; Optimization ; Pharmaceuticals ; Phenols ; Plant species ; Quality control ; Sodium phosphate ; Stationary phase ; Synergistic effect ; Thymol ; Triethylamine ; validation</subject><ispartof>Journal of liquid chromatography & related technologies, 2023-09, Vol.46 (6-10), p.168-179</ispartof><rights>2023 Taylor & Francis Group, LLC 2023</rights><rights>2023 Taylor & Francis Group, LLC</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c338t-284d76ce0bd16e650bafd257d84b5a763e77461c3eee7f63333f7de14c08bbee3</citedby><cites>FETCH-LOGICAL-c338t-284d76ce0bd16e650bafd257d84b5a763e77461c3eee7f63333f7de14c08bbee3</cites><orcidid>0000-0003-2870-5742 ; 0000-0002-5086-2923</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids></links><search><creatorcontrib>Muniz, Vanessa Morais</creatorcontrib><creatorcontrib>Chaves Júnior, José Venâncio</creatorcontrib><creatorcontrib>Aragão, Cícero Flávio Soares</creatorcontrib><creatorcontrib>Souza, Fábio Santos de</creatorcontrib><creatorcontrib>Sampaio, Fábio Correia</creatorcontrib><title>A HPLC method for simultaneous quantification of chlorhexidine and thymol using Box-Behnken design for robustness of the method assessment</title><title>Journal of liquid chromatography & related technologies</title><description>The antimicrobial chlorhexidine is considered the gold standard in dentistry. Thymol is a phenol found in the essential oils of various plant species and also stands out for its antimicrobial potential. Synergistic effects can be promoted by applying these two active pharmaceutical ingredients together in technological products, for example in controlled release microparticles. The objective of this work was to develop and validate an analytical methodology applying a Box-Behnken experimental design and using High Performance Liquid Chromatography capable of quantifying chlorhexidine and thymol simultaneously in a matrix including pharmaceutical excipients. After optimization, the mobile phase consisted of methanol and 0.03 M monobasic sodium phosphate buffer (60:40), with 0.4% triethylamine and octylsilane as the applied stationary phase. The method proved selective, even in the presence of chlorhexidine and thymol degradation products. For chlorhexidine, the method was linear from 4.8 to 19.2 µg/mL, and for thymol from 8.0 to 32.0 µg/mL. Accuracy was close to 100%, and the precision assessment yielded coefficient variation values of <5%. Being based on the Box-Behnken design, the method was robust and therefore validated for assisting in quality control processes involving these active pharmaceutical ingredients.</description><subject>Active control</subject><subject>Antiinfectives and antibacterials</subject><subject>Box-Behnken</subject><subject>Chlorhexidine</subject><subject>Coefficient of variation</subject><subject>Controlled release</subject><subject>Degradation products</subject><subject>Dentistry</subject><subject>Design of experiments</subject><subject>Essential oils</subject><subject>Experimental design</subject><subject>High performance liquid chromatography</subject><subject>HPLC</subject><subject>Ingredients</subject><subject>Ions</subject><subject>Liquid chromatography</subject><subject>Mathematical analysis</subject><subject>Microparticles</subject><subject>Optimization</subject><subject>Pharmaceuticals</subject><subject>Phenols</subject><subject>Plant species</subject><subject>Quality control</subject><subject>Sodium phosphate</subject><subject>Stationary phase</subject><subject>Synergistic effect</subject><subject>Thymol</subject><subject>Triethylamine</subject><subject>validation</subject><issn>1082-6076</issn><issn>1520-572X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kMtOxCAUhhujiePlEUxIXHcE2kLdOU68JZPoQhN3hJaDRVuYARpnXsGnlnF0K4sDOfnPd8KXZWcETwmu8UUqlGHOphTTYkop5fyS7mUTUlGcV5y-7qd3yuTb0GF2FMI7xoRXtJpkXzN0_7SYowFi5xTSzqNghrGP0oIbA1qN0kajTSujcRY5jdqud76DtVHGApJWodhtBtejMRj7hq7dOr-Gzn6ARQqCebM_UO-aMUQLIWwZsYO_jTKE1BzAxpPsQMs-wOnvfZy93N48z-_zxePdw3y2yNuiqGNO61Jx1gJuFGHAKtxIrWjFVV02leSsAM5LRtoCALhmRTqaKyBli-umASiOs_Mdd-ndaoQQxbsbvU0rRWJjXJOyZilV7VKtdyF40GLpzSD9RhAsttrFn3ax1S5-tae5q92csenfg_x0vlciyk2ypr20rQmi-B_xDVojjGg</recordid><startdate>20230915</startdate><enddate>20230915</enddate><creator>Muniz, Vanessa Morais</creator><creator>Chaves Júnior, José Venâncio</creator><creator>Aragão, Cícero Flávio Soares</creator><creator>Souza, Fábio Santos de</creator><creator>Sampaio, Fábio Correia</creator><general>Taylor & Francis</general><general>Taylor & Francis Ltd</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SE</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>7U7</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H8G</scope><scope>JG9</scope><scope>KR7</scope><scope>L7M</scope><scope>P64</scope><orcidid>https://orcid.org/0000-0003-2870-5742</orcidid><orcidid>https://orcid.org/0000-0002-5086-2923</orcidid></search><sort><creationdate>20230915</creationdate><title>A HPLC method for simultaneous quantification of chlorhexidine and thymol using Box-Behnken design for robustness of the method assessment</title><author>Muniz, Vanessa Morais ; 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subjects | Active control Antiinfectives and antibacterials Box-Behnken Chlorhexidine Coefficient of variation Controlled release Degradation products Dentistry Design of experiments Essential oils Experimental design High performance liquid chromatography HPLC Ingredients Ions Liquid chromatography Mathematical analysis Microparticles Optimization Pharmaceuticals Phenols Plant species Quality control Sodium phosphate Stationary phase Synergistic effect Thymol Triethylamine validation |
title | A HPLC method for simultaneous quantification of chlorhexidine and thymol using Box-Behnken design for robustness of the method assessment |
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