Liquid chromatography-tandem mass spectrometry analysis of urinary fluticasone propionate-17beta-carboxylic acid for monitoring compliance with inhaled-fluticasone propionate therapy

Nichole L. Korpi-Steiner, Brian C. Netzel, Jesse C. Seegmiller, John B. Hagan, Ravinder J. Singh

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Background: Inhaled 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. Experimental: Fluorometholone 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). Results: Linear 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. Conclusions: Measurement 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.

Original languageEnglish (US)
Pages (from-to)77-82
Number of pages6
JournalSteroids
Volume75
Issue number1
DOIs
StatePublished - Jan 1 2010

Keywords

  • Compliance
  • Inhaler
  • LC-MS/MS

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Liquid chromatography-tandem mass spectrometry analysis of urinary fluticasone propionate-17beta-carboxylic acid for monitoring compliance with inhaled-fluticasone propionate therapy'. Together they form a unique fingerprint.

  • Cite this