Quantification of fluticasone propionate in human plasma by LC–MS/MS and its application in the pharmacokinetic study of nasal spray at clinical doses

Abstract

We developed a method for quantifying fluticasone propionate (FP) using general-purpose liquid chromatography–tandem mass spectrometry equipment to measure the plasma concentration of FP for the pharmacokinetic study of FP following the administration of a prescribed nasal spray dose (100 μg). Using ammonium acetate (0.01 M)–formic acid (pH 2.9; 499:1, v/v) and methanol as the mobile phase, 3 pg/mL of FP was quantified. The relative error and standard deviation of the lower limit of quantification were <3.1%. The intra- and interday assay reproducibility was <3.5%. After 15 min of administering 200 μg FP nasal spray as the first dose, the FP concentration detected in the plasma of the two participants was 3.99 and 3.69 pg/mL. Subsequent doses of 100 μg FP were administered twice daily. The area under the plasma concentration–time curve values after 8–10 days of repeated administration of 100 μg of FP were approximately 1.6-fold higher than those achieved following a single administration of 200 μg of FP, which confirmed drug accumulation. The bioavailability of nasal FP was estimated to be 2% and 4%. This knowledge might help in reducing anxiety among patients who avoid using FP nasal spray, fearing its adverse effects.