An improved method for the determination of fluticasone propionate in human plasma

Therapeutic monitoring of the potent, highly lipophilic glucocorticoid, flu ticasone propionate (FP), was initially performed by a radioimmunoassay met hod. However an improved method with a lower limit of quantitation (LLOQ) o f 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 mu g twice daily. A sensitive and specific liquid chromat ographic, 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 C-13-labelled internal standard and was validated over a concentration range of 25-500 p g ml(-1). The method was shown to be specific, sensitive and reliable in th e analysis of clinical samples. The main advantages of this method over the radioimmunoassay method previously used were improved sensitivity, specifi city, ease of sample preparation and shortened analysis time. (C) 1999 Else vier Science B.V. All rights reserved.