title: Development of chiral methodologies by capillary electrophoresis with ultraviolet and mass spectrometry detection for duloxetine analysis in pharmaceutical formulations.
abstract: Two chiral methodologies were developed by capillary electrophoresis (CE) with UV and mass spectrometry (MS) detection to ensure the quality control of the drug duloxetine, commercialized as a pure enantiomer. Both methods were optimized to achieve a high baseline enantioresolution (Rs>2) and an acceptable precision (RSD values <5% for instrumental repeatability and <10% for intermediate precision). In addition to allow the unequivocal identification of duloxetine enantiomers, the CE-MS method improved the sensitivity with respect to the use of CE-UV (LOD 200 ng/mL by CE-UV and 20 ng/mL by CE-MS) enabling to detect 0.02% of duloxetine enantiomeric impurity. This is the lowest LOD value ever reported for this drug, being this work the first one enabling to accomplish with the ICH guidelines requirements. The developed methods were validated and applied for the first time to the analysis of four pharmaceutical formulations. The content of R-duloxetine in all these samples was below the detection limit and the amount of S-duloxetine was in good agreement with the labeled content, obtaining results by the two methods that did not differ significantly (p-values >0.05).
authors.affiliation: Department of Analytical Chemistry, Physical Chemistry and Chemical Engineering, University of Alcalá, Ctra. Madrid-Barcelona Km. 33.600, Alcalá de Henares, 28871 Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Sánchez-López
authors.affiliation: Department of Analytical Chemistry, Physical Chemistry and Chemical Engineering, University of Alcalá, Ctra. Madrid-Barcelona Km. 33.600, Alcalá de Henares, 28871 Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Montealegre
authors.affiliation: Department of Analytical Chemistry, Physical Chemistry and Chemical Engineering, University of Alcalá, Ctra. Madrid-Barcelona Km. 33.600, Alcalá de Henares, 28871 Madrid, Spain.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Marina
authors.affiliation: Department of Analytical Chemistry, Physical Chemistry and Chemical Engineering, University of Alcalá, Ctra. Madrid-Barcelona Km. 33.600, Alcalá de Henares, 28871 Madrid, Spain. Electronic address: antonio.crego@uah.es.
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Crego
mesh_terms: D000068736:Duloxetine Hydrochloride; D019075:Electrophoresis, Capillary / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*; D013237:Stereoisomerism; D013876:Thiophenes / Q000032:analysis*
chemical_list: D013876:Thiophenes; D000068736:Duloxetine Hydrochloride
keywords: Capillary electrophoresis; Duloxetine; Enantioseparation; Mass spectrometry; Partial filling technique