title: Green analytical method development for statin analysis.
abstract: Green analytical chemistry method was developed for pravastatin, fluvastatin and atorvastatin analysis. HPLC/DAD method using ethanol-based mobile phase with octadecyl-grafted silica with various grafting and related-column parameters such as particle sizes, core-shell and monolith was studied. Retention, efficiency and detector linearity were optimized. Even for column with particle size under 2 μm, the benefit of keeping efficiency within a large range of flow rate was not obtained with ethanol based mobile phase compared to acetonitrile one. Therefore the strategy to shorten analysis by increasing the flow rate induced decrease of efficiency with ethanol based mobile phase. An ODS-AQ YMC column, 50 mm × 4.6 mm, 3 μm was selected which showed the best compromise between analysis time, statin separation, and efficiency. HPLC conditions were at 1 mL/min, ethanol/formic acid (pH 2.5, 25 mM) (50:50, v/v) and thermostated at 40°C. To reduce solvent consumption for sample preparation, 0.5mg/mL concentration of each statin was found the highest which respected detector linearity. These conditions were validated for each statin for content determination in high concentrated hydro-alcoholic solutions. Solubility higher than 100mg/mL was found for pravastatin and fluvastatin, whereas for atorvastatin calcium salt the maximum concentration was 2mg/mL for hydro-alcoholic binary mixtures between 35% and 55% of ethanol in water. Using atorvastatin instead of its calcium salt, solubility was improved. Highly concentrated solution of statins offered potential fluid for per Buccal Per-Mucous(®) administration with the advantages of rapid and easy passage of drugs.
authors.affiliation: Université de Bordeaux, EA 4575 Analytical and Pharmaceutical Developments Applied to Neglected Diseases and Counterfeits, Bordeaux, France.
authors.forename: Amira Louiza
authors.initials: AL
authors.lastname: Assassi
authors.affiliation: Université de Bordeaux, EA 4575 Analytical and Pharmaceutical Developments Applied to Neglected Diseases and Counterfeits, Bordeaux, France.
authors.forename: Claude-Eric
authors.initials: CE
authors.lastname: Roy
authors.affiliation: THERA, 2 Route de la Poste, 33680 Le Temple, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Perovitch
authors.affiliation: ITEC Services, Cenon, France.
authors.forename: Jack
authors.initials: J
authors.lastname: Auzerie
authors.affiliation: Université de Bordeaux, EA 4575 Analytical and Pharmaceutical Developments Applied to Neglected Diseases and Counterfeits, Bordeaux, France.
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Hamon
authors.affiliation: Université de Bordeaux, EA 4575 Analytical and Pharmaceutical Developments Applied to Neglected Diseases and Counterfeits, Bordeaux, France. Electronic address: karen.gaudin@u-bordeaux.fr.
authors.forename: Karen
authors.initials: K
authors.lastname: Gaudin
mesh_terms: D000097:Acetonitriles; D000069059:Atorvastatin; D002851:Chromatography, High Pressure Liquid; D000431:Ethanol; D005229:Fatty Acids, Monounsaturated / Q000032:analysis; D000077340:Fluvastatin; D055772:Green Chemistry Technology; D006538:Heptanoic Acids / Q000032:analysis; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000032:analysis*; D007211:Indoles / Q000032:analysis; D017035:Pravastatin / Q000032:analysis; D011758:Pyrroles / Q000032:analysis; D012995:Solubility; D012997:Solvents
chemical_list: D000097:Acetonitriles; D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D011758:Pyrroles; D012997:Solvents; D000431:Ethanol; D000077340:Fluvastatin; D000069059:Atorvastatin; D017035:Pravastatin; C032159:acetonitrile
keywords: Ethanol; Green analytical chemistry; Solubility; Statins; Van Deemter