| Title | Liquid Chromatography-Tandem Mass Spectrometry Analysis of Urinary Fluticasone Propionate-17beta-Carboxylic Acid for Monitoring Compliance with Inhaled-Fluticasone Propionate Therapy. | | Author(s) | Korpi-Steiner NL, Netzel BC, Seegmiller JC, Hagan JB, Singh RJ | | Institution | Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1(st) Street S.W., Rochester, MN 55905. | | Source | Steroids 2009 Oct 30. | | Abstract | BACKGROUND: Inhaled corticosteroids including fluticasone propionate (FP) are the most effective treatment for persistent-asthma. Non-compliance ranging from 20-80% of treated patients is associated with substantial health care costs, morbidity and fatalities. A noninvasive test to assess FP treatment compliance is needed. The major metabolite of FP is FP-17beta-carboxylic acid (FP17betaCA) and is excreted in urine. This study demonstrates the development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay to measure FP17betaCA in urine and evaluation of FP17betaCA urinary elimination. EXPERIMENTAL: Fluorometholone was used as the internal standard. After acetonitrile precipitation, samples were extracted with dichloromethane, washed and dried. Reconstituted extract (60muL) was subjected to reversed-phase chromatography and positive-ion mode LC-MS/MS analysis. Assay precision, linearity, recovery and sample stability were determined. Elimination evaluation included measurement of FP17betaCA in urine collected daily from human subjects before (day 1), during treatment (days 2-5; Dose FP-110mug 2 puffs/day), and following cessation of FP therapy (days 6-14; n=4).
RESULTS: Linear range of the FP17betaCA assay was 10.3-9510 pg/mL. Limit of quantitation (LOQ) was 10.3 pg/mL and recovery ranged from 85.8-111.9%. Inter-assay CVs were 7.4-12.0% for FP17betaCA concentrations of 11.1-5117 pg/mL. Urine FP17betaCA was absent in subjects prior to FP therapy, detectable (180-1991 ng FP17betaCA/g creatinine) throughout the dosing period and reached below the LOQ at 6 days after therapy cessation.
CONCLUSIONS: Measurement of FP17betaCA by LC-MS/MS has acceptable analytical performance for clinical use. These data support the clinical utility of measuring FP17betaCA in urine to monitor patient compliance with FP therapy. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19883673 |
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