title: Optimization and validation of a fast supercritical fluid chromatography method for the quantitative determination of vitamin D3 and its related impurities.
abstract: In the uprising context of green analytical chemistry, Supercritical Fluid Chromatography (SFC) is often suggested as an alternative to Normal Phase Liquid Chromatography. Indeed, SFC provides fast, efficient and green separations. In this report, the quantitative performances of SFC were challenged on a real-life case study: the Quality Control (QC) of vitamin D3. A rapid and green SFC method was optimized thanks to the Design of Experiments-Design Space (DoE-DS) methodology. It provided robust and high quality separation of the compounds within a 2min timeframe, using a gradient of ethanol as co-solvent of the carbon dioxide. The analytical method was fully validated according to the total error approach, demonstrating the compliance of the method to the specifications of U.S. Pharmacopeia (USP: 97.0-103.0%) and European Pharmacopeia (EP: 97.0-102.0%) for an interval of [50-150%] of the target concentration. In order to allow quantification of impurities using vitamin D3 as an external standard in SFC-UV, correction factors were determined and verified during method validation. Thus, accurate quantification of impurities was demonstrated at the specified levels (0.1 and 1.0% of the main compound) for a 70.0-130.0% dosing range. This work demonstrates the validity of an SFC method for the QC of vitamin D3 raw material and its application to real samples. Therefore, it supports the switch to a greener and faster separative technique as an alternative to NPLC in the pharmaceutical industry.
authors.affiliation: University of Liège (ULg), CIRM, Laboratory of Analytical Chemistry, 15 Avenue Hippocrate, B36, B-4000 Liège, Belgium. Electronic address: Bertyl.Andri@ulg.ac.be.
authors.forename: B
authors.initials: B
authors.lastname: Andri
authors.affiliation: University of Liège (ULg), CIRM, Laboratory of Analytical Chemistry, 15 Avenue Hippocrate, B36, B-4000 Liège, Belgium; Arlenda s.a., Chaussée verte, 93, B-4470 Saint-Georges-sur-meuse, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Lebrun
authors.affiliation: University of Liège (ULg), CIRM, Laboratory of Analytical Chemistry, 15 Avenue Hippocrate, B36, B-4000 Liège, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Dispas
authors.affiliation: Galephar Research Center M/F, 39 Rue du parc industriel, B-6900 Marche en Famenne, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Klinkenberg
authors.affiliation: Galephar Research Center M/F, 39 Rue du parc industriel, B-6900 Marche en Famenne, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Streel
authors.affiliation: University of Liège (ULg), CIRM, Laboratory of Analytical Chemistry, 15 Avenue Hippocrate, B36, B-4000 Liège, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Ziemons
authors.affiliation: University of Liège (ULg), CIRM, Laboratory of Analytical Chemistry, 15 Avenue Hippocrate, B36, B-4000 Liège, Belgium.
authors.forename: R D
authors.initials: RD
authors.lastname: Marini
authors.affiliation: University of Liège (ULg), CIRM, Laboratory of Analytical Chemistry, 15 Avenue Hippocrate, B36, B-4000 Liège, Belgium.
authors.forename: Ph
authors.initials: P
authors.lastname: Hubert
mesh_terms: D002762:Cholecalciferol / Q000032:analysis* / Q000737:chemistry / Q000592:standards; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D004340:Drug Contamination; D015203:Reproducibility of Results
chemical_list: D002762:Cholecalciferol
keywords: Accuracy profile; Design space; Green analytical chemistry; Method validation; SFC; Vitamin D3