title: Optimization of a validated stability-indicating RP-LC method for the determination of fulvestrant from polymeric based nanoparticle systems, drugs and biological samples.
abstract: Fulvestrant is used for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy. Several reversed-phase columns with variable silica materials, diameters, lengths, etc., were tested for the optimization study. A good chromatographic separation was achieved using a Waters X-Terra RP(18) column (250 × 4.6 mm i.d. × 5 µm) and a mobile phase, consisting of a mixture of acetonitrile-water (65:35; v/v) containing phosphoric acid (0.1%). The separation was carried out 40 °C with detection at 215 nm.The calibration curves were linear over the concentration range between 1.0-300 and 1.0-200 µg/mL for standard solutions and biological media, respectively. The proposed method is accurate and reproducible. Forced degradation studies were also realized. This fully validated method allows the direct determination of fulvestrant in dosage form and biological samples. The average recovery of the added fulvestrant amount in the samples was between 98.22 and 104.03%. The proposed method was also applied for the determination of fulvestrant from the polymeric-based nanoparticle systems. No interference from using polymers and other excipients was observed in in vitro drug release studies. Therefore an incorporation efficiency of fulvestrant-loaded nanoparticle could be determined accurately and specifically.
authors.affiliation: Ankara University, Faculty of Pharmacy, Department of Analytical Chemistry, Ankara, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Gumustas
authors.forename: Ceyda Tuba
authors.initials: CT
authors.lastname: Sengel-Turk
authors.forename: Canan
authors.initials: C
authors.lastname: Hascicek
authors.forename: Sibel A
authors.initials: SA
authors.lastname: Ozkan
mesh_terms: D056148:Chromatography, Reverse-Phase / Q000379:methods*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D000077267:Fulvestrant; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid; D057230:Limit of Detection; D016014:Linear Models; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols; D011098:Polyglactin 910; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015203:Reproducibility of Results
chemical_list: C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D000077267:Fulvestrant; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D004958:Estradiol
keywords: RP-LC; biological samples; fulvestrant; nanoparticles; optimization; validation