Liquid chromatography-tandem mass spectrometry analysis of urinary fluticasone propionate-17beta-carboxylic acid for monitoring compliance with inhaled-fluticasone propionate therapy |
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Authors: | Nichole L. Korpi-Steiner Jesse C. Seegmiller Ravinder J. Singh |
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Affiliation: | a Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st Street S.W., Rochester, MN 55905, United States b Department of Internal Medicine, Mayo Clinic, 200 1st Street S.W., Rochester, MN 55905, United States |
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Abstract: | BackgroundInhaled corticosteroids including fluticasone propionate (FP) are the most effective treatment for persistent-asthma. Noncompliance ranging from 20% to 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 (FP17βCA) and is excreted in urine. This study demonstrates the development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay to measure FP17βCA in urine and evaluation of FP17βCA urinary elimination.ExperimentalFluorometholone was used as the internal standard. After acetonitrile precipitation, samples were extracted with dichloromethane, washed and dried. Reconstituted extract (60 μL) 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 FP17βCA in urine collected daily from human subjects before (day 1), during treatment (days 2-5; dose FP-110 μg 2 puffs/day), and following cessation of FP therapy (days 6-14; n = 4).ResultsLinear range of the FP17βCA assay was 10.3-9510 pg/mL. Limit of quantitation (LOQ) was 10.3 pg/mL and recovery ranged from 85.8% to 111.9%. Inter-assay CVs were 7.4-12.0% for FP17βCA concentrations of 11.1-5117 pg/mL. Urine FP17βCA was absent in subjects prior to FP therapy, detectable (180-1991 ng FP17βCA/g creatinine) throughout the dosing period and reached below the LOQ at 6 days after therapy cessation.ConclusionsMeasurement of FP17βCA by LC-MS/MS has acceptable analytical performance for clinical use. These data support the clinical utility of measuring FP17βCA in urine to monitor patient compliance with FP therapy. |
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Keywords: | LC-MS/MS Compliance Inhaler |
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