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 language | English (US) |
|---|---|
| Pages (from-to) | 77-82 |
| Number of pages | 6 |
| Journal | Steroids |
| Volume | 75 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2010 |
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Keywords
- Compliance
- Inhaler
- LC-MS/MS
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
- Endocrinology
- Molecular Biology
- Organic Chemistry
- Pharmacology
Cite this
Liquid chromatography-tandem mass spectrometry analysis of urinary fluticasone propionate-17beta-carboxylic acid for monitoring compliance with inhaled-fluticasone propionate therapy. / Korpi-Steiner, Nichole L.; Netzel, Brian C.; Seegmiller, Jesse C.; Hagan, John B.; Singh, Ravinder Jit.
In: Steroids, Vol. 75, No. 1, 01.2010, p. 77-82.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Liquid chromatography-tandem mass spectrometry analysis of urinary fluticasone propionate-17beta-carboxylic acid for monitoring compliance with inhaled-fluticasone propionate therapy
AU - Korpi-Steiner, Nichole L.
AU - Netzel, Brian C.
AU - Seegmiller, Jesse C.
AU - Hagan, John B.
AU - Singh, Ravinder Jit
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
KW - Compliance
KW - Inhaler
KW - LC-MS/MS
UR - http://www.scopus.com/inward/record.url?scp=71849102501&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=71849102501&partnerID=8YFLogxK
U2 - 10.1016/j.steroids.2009.10.009
DO - 10.1016/j.steroids.2009.10.009
M3 - Article
C2 - 19883673
AN - SCOPUS:71849102501
VL - 75
SP - 77
EP - 82
JO - Steroids
JF - Steroids
SN - 0039-128X
IS - 1
ER -