title: Quantitative determination of salbutamol sulfate impurities using achiral supercritical fluid chromatography.
abstract: In the last years, supercritical fluid chromatography has largely been acknowledged as a singular and performing technique in the field of separation sciences. Recent studies highlighted the interest of SFC for the quality control of pharmaceuticals, especially in the case of the determination of the active pharmaceutical ingredient (API). Nevertheless, quality control requires also the determination of impurities. The objectives of the present work were to (i) demonstrate the interest of SFC as a reference technique for the determination of impurities in salbutamol sulfate API and (ii) to propose an alternative to a reference HPLC method from the European Pharmacopeia (EP) involving ion-pairing reagent. Firstly, a screening was carried out to select the most adequate and selective stationary phase. Secondly, in the context of robust optimization strategy, the method was developed using design space methodology. The separation of salbutamol sulfate and related impurities was achieved in 7min, which is seven times faster than the LC-UV method proposed by European Pharmacopeia (total run time of 50min). Finally, full validation using accuracy profile approach was successfully achieved for the determination of impurities B, D, F and G in salbutamol sulfate raw material. The validated dosing range covered 50 to 150% of the targeted concentration (corresponding to 0.3% concentration level), LODs close to 0.5μg/mL were estimated. The SFC method proposed in this study could be presented as a suitable fast alternative to EP LC method for the quantitative determination of salbutamol impurities.
authors.affiliation: University of Liege (ULg), CIRM, Laboratory of Analytical Chemistry, Liège, Belgium. Electronic address: amandine.dispas@ulg.ac.be.
authors.forename: Amandine
authors.initials: A
authors.lastname: Dispas
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, CMU-Rue Michel Servet, 1-, 1211 Geneva 4, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Desfontaine
authors.affiliation: University of Liege (ULg), CIRM, Laboratory of Analytical Chemistry, Liège, Belgium.
authors.forename: Bertyl
authors.initials: B
authors.lastname: Andri
authors.affiliation: University of Liege (ULg), CIRM, Laboratory of Analytical Chemistry, Liège, Belgium; Arlenda s.a., Liège, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lebrun
authors.affiliation: Novartis Pharma AG, Technical R&D, Chemical and Analytical Development, Basel, CH4056, Switzerland.
authors.forename: Dorina
authors.initials: D
authors.lastname: Kotoni
authors.affiliation: Novartis Pharma AG, Technical R&D, Chemical and Analytical Development, Basel, CH4056, Switzerland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Clarke
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, CMU-Rue Michel Servet, 1-, 1211 Geneva 4, Switzerland.
authors.forename: Davy
authors.initials: D
authors.lastname: Guillarme
authors.affiliation: University of Liege (ULg), CIRM, Laboratory of Analytical Chemistry, Liège, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hubert
mesh_terms: D000420:Albuterol / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000592:standards; D025924:Chromatography, Supercritical Fluid / Q000379:methods* / Q000592:standards; D004340:Drug Contamination; D013237:Stereoisomerism
chemical_list: D000420:Albuterol
keywords: Impurity profiling; Method validation; Quality by design (QbD); Salbutamol sulfate; Supercritical fluid chromatography (SFC); Total error approach