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However, the complexity of plant matrices and structural similarity between cannabinoids make analytical development a challenging task. Thus, the application of analytical quality by design (AQbD)\u2010driven approaches can favour the development of fit\u2010for\u2010purpose methods.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To develop a high\u2010performance liquid chromatography diode array detector (HPLC\u2010DAD) method for simultaneous quantification of cannabidiol, \u0394\n                      <jats:sup>9<\/jats:sup>\n                      \u2010tetrahydrocannabinol, cannabidiolic acid, tetrahydrocannabinolic acid, and cannabinol in\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>C. sativa<\/jats:italic>\n                      <\/jats:styled-content>\n                      by applying an AQbD\u2010driven approach.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Critical method attributes (CMA) were established following the analytical target profile. Critical method variables (CMV) were categorised based on risk assessment and literature review. Selected CMV regarding sample preparation and chromatographic conditions were optimised using response surface methodology (RSM). The working point was estimated by multiple response optimisation using Deringer's desirability function. The validity of the optimal conditions was confirmed experimentally. Method validation was performed according to ANVISA and ICH guidelines. Relative response factors (RRFs) were also determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Discussion<\/jats:title>\n                    <jats:p>\n                      Baseline resolution of 12 major cannabinoids was achieved in a 35\u2009min chromatographic analysis. All experimental responses obtained during confirmatory analyses were within the prediction intervals (PI\n                      <jats:sub>95%<\/jats:sub>\n                      ). Method's selectivity, linearity (10\u2013100\u2009\u03bcg\/mL), precision, bias, extraction recovery, and ruggedness were satisfactorily demonstrated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The application of an AQbD\u2010driven approach allowed for a better understanding of the effects of the ensemble of CMV on the analyte's behaviour, enabling the definition of appropriate conditions to ensure consistent achievement of the intended method's performance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pca.3154","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T23:11:29Z","timestamp":1655939489000},"page":"999-1017","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["DoE\u2010assisted development and validation of a stability\u2010indicating HPLC\u2010DAD method for simultaneous determination of five cannabinoids in\n                    <scp>\n                      <i>Cannabis sativa<\/i>\n                    <\/scp>\n                    L. based on analytical quality by design (AQbD) concept"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1003-2458","authenticated-orcid":false,"given":"Ma\u00edra Ribeiro","family":"de Souza","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de An\u00e1lises e Pesquisas em Toxicologia, Faculdade de Farm\u00e1cia Universidade Federal do Rio Grande do Sul (UFRGS)  Porto Alegre RS Brazil"},{"name":"Laborat\u00f3rio de Farmacognosia e Controle da Qualidade de Fitoter\u00e1picos, Faculdade de Farm\u00e1cia Universidade Federal do Rio Grande do Sul (UFRGS)  Porto Alegre RS Brazil"},{"name":"Ag\u00eancia Nacional de Vigil\u00e2ncia Sanit\u00e1ria (ANVISA)  Bras\u00edlia DF Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Koetz","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacognosia e Controle da Qualidade de Fitoter\u00e1picos, Faculdade de Farm\u00e1cia Universidade Federal do Rio Grande do Sul (UFRGS)  Porto Alegre RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2561-2647","authenticated-orcid":false,"given":"Renata Pereira","family":"Limberger","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de An\u00e1lises e Pesquisas em Toxicologia, Faculdade de Farm\u00e1cia Universidade Federal do Rio Grande do Sul (UFRGS)  Porto Alegre RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1928-3771","authenticated-orcid":false,"given":"Am\u00e9lia Teresinha","family":"Henriques","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacognosia e Controle da Qualidade de Fitoter\u00e1picos, Faculdade de Farm\u00e1cia Universidade Federal do Rio Grande do Sul (UFRGS)  Porto Alegre RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,22]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"World Health Organization.Cannabis and Cannabis Resin. 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