title: An improved method for the determination of fluticasone propionate in human plasma.
abstract: Therapeutic monitoring of the potent, highly lipophilic glucocorticoid, fluticasone propionate (FP), was initially performed by a radioimmunoassay method. However an improved method with a lower limit of quantitation (LLOQ) of at least 25 pg per ml (pg/ml(-1)) was needed to measure the low levels of FP present in human plasma following inhalation administration of doses in the range 50-250 microg twice daily. A sensitive and specific liquid chromatographic, tandem mass spectrometric method (LC-MS/MS) with automated solid phase extraction (SPE) was developed and validated. Fluticasone propionate was extracted from plasma using Bond Elut C18 cartridges and analysed using reverse-phase chromatography with atmospheric pressure chemical ionisation followed by selective reaction monitoring. The method used a 13C-labelled internal standard and was validated over a concentration range of 25-500 pg/ml(-1). The method was shown to be specific, sensitive and reliable in the analysis of clinical samples. The main advantages of this method over the radioimmunoassay method previously used were improved sensitivity, specificity, ease of sample preparation and shortened analysis time.
authors.affiliation: Covance Laboratories Ltd, Harrogate, N. Yorks, UK.
authors.forename: L
authors.initials: L
authors.lastname: Laugher
authors.forename: T G
authors.initials: TG
authors.lastname: Noctor
authors.forename: A
authors.initials: A
authors.lastname: Barrow
authors.forename: J M
authors.initials: JM
authors.lastname: Oxford
authors.forename: T
authors.initials: T
authors.lastname: Phillips
mesh_terms: D000730:Androstadienes / Q000008:administration & dosage / Q000097:blood*; D000893:Anti-Inflammatory Agents / Q000097:blood*; D000068298:Fluticasone; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D011863:Radioimmunoassay; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D000068298:Fluticasone