Chiral capillary zone electrophoresis in enantioseparation and analysis of cinacalcet impurities: Use of Quality by Design principles in method development
Autor: | Mercedes Villar-Navarro, Roberto Gotti, Sandra Furlanetto, Alessandro Giuffrida, Claudia Caprini, Benedetta Pasquini, Serena Orlandini, Massimo Del Bubba, Michal Douša |
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Přispěvatelé: | Pasquini, Benedetta, Orlandini, Serena, Villar-Navarro, Mercede, Caprini, Claudia, Del Bubba, Massimo, Douša, Michal, Giuffrida, Alessandro, Gotti, Roberto, Furlanetto, Sandra |
Rok vydání: | 2018 |
Předmět: |
Analyte
02 engineering and technology Electrolyte 01 natural sciences Biochemistry Risk Assessment Quality by Design Analytical Chemistry Matrix (chemical analysis) Method operable design region Capillary electrophoresis Impuritie Probability Chromatography Chemistry gamma-Cyclodextrin 010401 analytical chemistry Organic Chemistry beta-Cyclodextrins beta-Cyclodextrin Electrophoresis Capillary Stereoisomerism General Medicine Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Chiral separation 0104 chemical sciences Capillary electrophoresi Capillary length Cinacalcet Hydrochloride Solvent Solvents Cinacalcet Enantiomer 0210 nano-technology Drug Contamination Monte Carlo Method gamma-Cyclodextrins |
Zdroj: | Journal of chromatography. A. 1568 |
ISSN: | 1873-3778 |
Popis: | A capillary electrophoresis method for the simultaneous determination of the enantiomeric purity and of impurities of the chiral calcimimetic drug cinacalcet hydrochloride has been developed following Quality by Design principles. The scouting phase was aimed to select the separation operative mode and to identify a suitable chiral selector. Among the tested cyclodextrins, (2-carboxyethyl)-β-cyclodextrin and (2-hydroxypropyl)-γ-cyclodextrin (HPγCyD) showed good chiral resolving capabilities. The selected separation system was solvent-modified capillary zone electrophoresis with the addition of HPγCyD and methanol. Voltage, buffer pH, methanol concentration and HPγCyD concentration were investigated as critical method parameters by a multivariate strategy. Critical method attributes were represented by enantioresolution and analysis time. A Box-Behnken Design allowed the contour plots to be drawn and quadratic and interaction effects to be highlighted. The Method Operable Design Region (MODR) was identified by applying Monte-Carlo simulations and corresponded to the multidimensional zone where both the critical method attributes fulfilled the requirements with a desired probability π ≥ 90%. The working conditions, with the MODR limits, corresponded to the following: capillary length, 48.5 cm; temperature, 18 °C; voltage, 26 kV (26–27 kV); background electrolyte, 150 mM phosphate buffer pH 2.70 (2.60–2.80), 3.1 mM (3.0–3.5 mM) HPγCyD; 2.00% (0.00–8.40%) v/v methanol. Robustness testing was carried out by a Plackett-Burman matrix and finally a method control strategy was defined. The complete separation of the analytes was obtained in about 10 min. The method was validated following the International Council for Harmonisation guidelines and was applied for the analysis of a real sample of cinacalcet hydrochloride tablets. |
Databáze: | OpenAIRE |
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