title: Using an innovative combination of quality-by-design and green analytical chemistry approaches for the development of a stability indicating UHPLC method in pharmaceutical products.
abstract: An innovative combination of green chemistry and quality by design (QbD) approach is presented through the development of an UHPLC method for the analysis of the main degradation products of dextromethorphan hydrobromide. QbD strategy was integrated to the field of green analytical chemistry to improve method understanding while assuring quality and minimizing environmental impacts, and analyst exposure. This analytical method was thoroughly evaluated by applying risk assessment and multivariate analysis tools. After a scouting phase aimed at selecting a suitable stationary phase and an organic solvent in accordance with green chemistry principles, quality risk assessment tools were applied to determine the critical process parameters (CPPs). The effects of the CPPs on critical quality attributes (CQAs), i.e., resolutions, efficiencies, and solvent consumption were further evaluated by means of a screening design. A response surface methodology was then carried out to model CQAs as function of the selected CPPs and the optimal separation conditions were determined through a desirability analysis. Resulting contour plots enabled to establish the design space (DS) (method operable design region) where all CQAs fulfilled the requirements. An experimental validation of the DS proved that quality within the DS was guaranteed; therefore no more robustness study was required before the validation. Finally, this UHPLC method was validated using the concept of total error and was used to analyze a pharmaceutical drug product.
authors.affiliation: Analytical Innovation, Unither Développement, Avenue Toussaint Catros, 33185 Le Haillan, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Boussès
authors.affiliation: Bordeaux University, EA 4575 Analytical and Pharmaceutical Developments Applied to Neglected Diseases and Counterfeits, 146, rue Léo Saignat, 33076. Electronic address: ludivine.ferey@u-bordeaux.fr.
authors.forename: Ludivine
authors.initials: L
authors.lastname: Ferey
authors.affiliation: Analytical Innovation, Unither Développement, Avenue Toussaint Catros, 33185 Le Haillan, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Vedrines
authors.affiliation: Bordeaux University, EA 4575 Analytical and Pharmaceutical Developments Applied to Neglected Diseases and Counterfeits, 146, rue Léo Saignat, 33076.
authors.forename: Karen
authors.initials: K
authors.lastname: Gaudin
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003915:Dextromethorphan / Q000032:analysis*; D004340:Drug Contamination; D055772:Green Chemistry Technology / Q000379:methods*; D008956:Models, Chemical; D015999:Multivariate Analysis; D004364:Pharmaceutical Preparations / Q000032:analysis*; D011786:Quality Control; D012044:Regression Analysis; D015203:Reproducibility of Results; D018570:Risk Assessment
chemical_list: D004364:Pharmaceutical Preparations; D003915:Dextromethorphan
keywords: Accuracy profile; Dextromethorphan; Experimental designs; Green chemistry; Quality-by-design; Robustness