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Title: | Expediting Disulfiram Assays through a Systematic Analytical Quality by Design Approach | Authors: | Basso, João Ramos, Maria Luísa Pais, Alberto Vitorino, Rui Fortuna, Ana Vitorino, Carla |
Keywords: | AQbD; cancer; central composite design; copper diethyldithiocarbamate; disulfiram; lipid nanoparticles; liquid chromatography; method optimization; method robustness; MODR | Issue Date: | 2021 | Publisher: | MDPI | Project: | UIDB/04501/2020 POCI-01-0145-FEDER-007628 UID/IC/00051/2019 UIDB/50006/2020 CENTRO-01-0145-FEDER-03075 UID/QUI/00313/2020 FCT - individual fellowship grant (IF/00286/2015 FCT - PhD research grant (SFRH/BD/149138/2019) FCT grants REEQ/481/QUI/2006, RECI/QEQQFI/ 0168/2012, CENTRO-07-CT62-FEDER-002012 |
Serial title, monograph or event: | Chemosensors | Volume: | 9 | Issue: | 7 | Abstract: | An Analytical Quality by Design (AQbD) approach is presented, aiming at the development and validation of an HPLC method for the quantification of disulfiram and copper diethyldithiocarbamate in lipid nanoparticles. Following the definition of the analytical target profile (ATP), encompassing the critical analytical attributes (CAA), a two-level risk assessment strategy (Ishikawa diagram—failure mode and effect analysis (FMEA)) was employed to identify the critical method parameters (CMPs) with an extensive impact on method performance. The behavior of the CMPs (flow rate and mobile phase composition) was further characterized by experimental design, resorting to a face-centered central composite design (FcCCD). Statistical modeling, response surface analysis, and Monte Carlo simulations led to the definition of the Method Operable Design Region (MODR), associated with a negligible risk of failing the predefined CAA specifications. The optimal method was validated according to international regulatory recommendations. Apart from guaranteeing linearity, accuracy, precision, specificity, robustness, and stability, these conditions were found to be suitable for analysis using a different HPLC column and equipment. In a nutshell, the development and optimization strategies, under the comprehensive framework of AQbD, provided an effective, simple, rapid, reliable, and flexible method for routine analysis of the compounds in research or industrial environments. | URI: | https://hdl.handle.net/10316/103829 | ISSN: | 2227-9040 | DOI: | 10.3390/chemosensors9070172 | Rights: | openAccess |
Appears in Collections: | FFUC- Artigos em Revistas Internacionais I&D CQC - Artigos em Revistas Internacionais I&D IBILI - Artigos em Revistas Internacionais |
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