Analytical Quality By Design Methodology For Botanical Raw Material Analysis: A Case Study of Flavonoids in Genkwa Flos

Analytical Quality By Design Methodology For Botanical Raw Material Analysis: A Case Study of Flavonoids in Genkwa Flos | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Analytical Quality By Design Methodology For Botanical Raw Material Analysis: A Case Study of Flavonoids in Genkwa Flos Min Kyoung Kim, Sang Cheol Park, Geonha Park, Eunjung Choi, Yura Ji, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-225793/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract The present study introduces a systematic approach using analytical quality by design (AQbD) methodology for the development of a qualified liquid chromatographic analytical method, which is a challenge in herbal medicinal products due to the intrinsic complex components of botanical sources. The ultra-high-performance liquid chromatography-photodiode array-mass spectrometry (UHPLC-PDA-MS) technique for eleven flavonoids in Genkwa Flos was utilized through the entire analytical processes, from the risk assessment study to the factor screening test, and finally in method optimization employing central composite design (CCD). In this approach, column temperature and mobile solvent slope were found to be critical method parameters (CMPs) and each of the eleven flavonoid peak’s resolution values were used as critical method attributes (CMAs) through data mining conversion formulas. An optimum chromatographic method in the design space was calculated by mathematical and response surface methodology (RSM). A validation study was also performed successfully for apigenin 7- O -glucuronide, apigenin, and genkwanin. In conclusion, the present design-based approach provide a systematic platform that can be effectively applied to ensure pharmaceutically qualified analytical data from complex natural products based botanical drug. Drug Discovery, Design, & Development analytical quality by design (AQbD) central composite design (CCD) critical method parameters (CMPs) Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Full Text Additional Declarations No competing interests reported. Supplementary Files ScientificreportsSupplementaryinformation.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 09 Apr, 2021 Reviews received at journal 20 Mar, 2021 Reviewers agreed at journal 17 Mar, 2021 Reviewers invited by journal 28 Feb, 2021 Editor assigned by journal 28 Feb, 2021 Editor invited by journal 15 Feb, 2021 Submission checks completed at journal 15 Feb, 2021 First submitted to journal 09 Feb, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-225793","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":11901245,"identity":"83ef2ad9-780d-4fc3-95f1-e884e11bb133","order_by":0,"name":"Min Kyoung Kim","email":"","orcid":"","institution":"Kyung Hee University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Min","middleName":"Kyoung","lastName":"Kim","suffix":""},{"id":11901248,"identity":"e20823c5-2dfd-4b85-82da-edf36f79be9b","order_by":1,"name":"Sang Cheol Park","email":"","orcid":"","institution":"Kyung Hee University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sang","middleName":"Cheol","lastName":"Park","suffix":""},{"id":11901249,"identity":"12d73061-7a04-4b7f-8576-8ce9db7fba6a","order_by":2,"name":"Geonha Park","email":"","orcid":"","institution":"Kyung Hee University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Geonha","middleName":"","lastName":"Park","suffix":""},{"id":11901250,"identity":"40920594-107d-4e87-b62e-e953bab3f881","order_by":3,"name":"Eunjung Choi","email":"","orcid":"","institution":"Kyung Hee University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Eunjung","middleName":"","lastName":"Choi","suffix":""},{"id":11901251,"identity":"0e702580-8ac7-42b8-9018-84876567addf","order_by":4,"name":"Yura Ji","email":"","orcid":"","institution":"Kyung Hee University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yura","middleName":"","lastName":"Ji","suffix":""},{"id":11901252,"identity":"e7cd5f29-e84b-4805-9713-772a230b9f4a","order_by":5,"name":"Young Pyo Jang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxklEQVRIiWNgGAWjYHCCBCC2MTBAcIjTkkaaFhA4TIIWg9sNDz8X/DpvbC6RwPjhB0NaPmEtdw4kS8/su21mOSOBWbKHIceygaCWGwkJ0rw9t22ADAZpBoYKA8K23EhI/s3bcw6khfk3sVrSpHl+HDADMtiAtuQQ1iJ550CaNW9DsrHBmYdtlj0GaYS18N3uSb7N88fOcMPx5MM3flQkE9aicIMngYGxDcRkbAC6k6AGBgb5GewHGBj+EKFyFIyCUTAKRi4AACM6PnoaXvTVAAAAAElFTkSuQmCC","orcid":"","institution":"Kyung Hee University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Young","middleName":"Pyo","lastName":"Jang","suffix":""}],"badges":[],"createdAt":"2021-02-09 07:44:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-225793/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-225793/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":6317517,"identity":"104d618d-62a2-4f0e-9c1e-31ad26bf3bed","added_by":"auto","created_at":"2021-02-24 18:19:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":114878,"visible":true,"origin":"","legend":"Representative UHPLC chromatogram of Genkwa Flos extract tagged with characteristic 11 flavonoid peaks (A) and their chemical structures (B). Kinetex-C18 50 ⅹ 2.1 mm, 1.7 μm column; mobile phase-A: 0.1% formic acid in water, mobile phase-B: acetonitrile; 254 nm detection; column temperature 28℃; 0.35 mL/min; gradient Time (min):%B, 0:10, 13:45, 13.5:100, 14:10, 15:10 used for the chromatogram.","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-225793/v1/b95d3409a6ad43b77f12eeda.png"},{"id":6318144,"identity":"3365cc62-ee6f-439b-944a-7f898d10c7fa","added_by":"auto","created_at":"2021-02-24 18:22:24","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":63545,"visible":true,"origin":"","legend":"Ishikawa Fishbone in Six Sigma of the UHPLC-PDA performance.","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-225793/v1/a1b683ac00d756731b3aae9d.png"},{"id":6317518,"identity":"51d22147-da33-4261-8714-398e4ed9b697","added_by":"auto","created_at":"2021-02-24 18:19:24","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":69024,"visible":true,"origin":"","legend":"Pareto Chart (A) and Main Effect Plots (B) obtained during factor screening of critical method attributes (CMAs), Yn; peak numbers.","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-225793/v1/fbeec878a042c9b2741e1ba8.png"},{"id":6316980,"identity":"a85948c2-d3e7-48f9-bcae-046c85cf9489","added_by":"auto","created_at":"2021-02-24 18:16:23","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":61324,"visible":true,"origin":"","legend":"Pareto Chart (A), Main Effect Plots (B), and Interaction Plots (C) obtained during center composite design (CCD) studies of critical method attributes (CMAs), Ysum; summarizes the eleven 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The ultra-high-performance liquid chromatography-photodiode array-mass spectrometry (UHPLC-PDA-MS) technique for eleven flavonoids in Genkwa Flos was utilized through the entire analytical processes, from the risk assessment study to the factor screening test, and finally in method optimization employing central composite design (CCD). In this approach, column temperature and mobile solvent slope were found to be critical method parameters (CMPs) and each of the eleven flavonoid peak\u0026rsquo;s resolution values were used as critical method attributes (CMAs) through data mining conversion formulas. An optimum chromatographic method in the design space was calculated by mathematical and response surface methodology (RSM). A validation study was also performed successfully for apigenin 7-\u003cem\u003eO\u003c/em\u003e-glucuronide, apigenin, and genkwanin. In conclusion, the present design-based approach provide a systematic platform that can be effectively applied to ensure pharmaceutically qualified analytical data from complex natural products based botanical drug.\u003c/p\u003e","manuscriptTitle":"Analytical Quality By Design Methodology For Botanical Raw Material Analysis: A Case Study of Flavonoids in Genkwa Flos","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-02-24 18:16:20","doi":"10.21203/rs.3.rs-225793/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2021-04-09T09:08:49+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-03-20T23:22:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"048043b9-fd14-435b-a2b1-dcdbcda629c4","date":"2021-03-17T22:31:45+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-03-01T02:00:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2021-03-01T01:49:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-02-15T06:25:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-02-15T06:20:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2021-02-09T07:43:12+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a3c406bf-69ca-4714-854e-0abd84f7d776","owner":[],"postedDate":"February 24th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":2600075,"name":"Drug Discovery, Design, \u0026 Development"}],"tags":[],"updatedAt":"2021-05-18T06:29:08+00:00","versionOfRecord":[],"versionCreatedAt":"2021-02-24 18:16:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-225793","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-225793","identity":"rs-225793","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}