Development and validation of an assay for quantifying budesonide in dried blood spots collected from extremely low gestational age neonates

Joseph E. Rower, David J. Anderson, Catherine M. Sherwin, Christopher A. Reilly, Philip L. Ballard, Cynthia (Cindy) McEvoy, Diana G. Wilkins

Research output: Contribution to journalArticle

Abstract

Budesonide is a potential therapeutic option for the prevention of bronchopulmonary dysplasia in mechanically ventilated premature neonates. The dose and concentrations of budesonide that drive effective prophylaxis are unknown, due in part to the difficulty in obtaining serial blood samples from this fragile population. Of primary concern is the limited total blood volume available for collection for the purposes of a pharmacokinetic study. Dried blood spots (DBS), which require the collection of <200 μL whole blood to fill an entire card, are an attractive low-blood volume alternative to traditional venipuncture sampling. We describe a simple and sensitive method for determining budesonide concentrations in DBS using an ultra-high-performance liquid chromatography – tandem mass spectrometry assay. Budesonide was liberated from a single 6 mm punch using a basified methyl tert-butyl ether extraction procedure. The assay was determined to be accurate and precise in the dynamic range of 1 to 50 ng/mL. The validated assay was then successfully applied to DBS collected as part of a multi-center, dose-escalation study of budesonide administered in surfactant via intra-tracheal instillation to premature neonates between 23 and 28 weeks gestational age. These findings show that DBS are a useful technique for collecting pharmacokinetic samples in premature neonates and other pediatric populations.

Original languageEnglish (US)
Pages (from-to)7-14
Number of pages8
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume167
DOIs
StatePublished - Apr 15 2019

Fingerprint

Budesonide
Gestational Age
Assays
Blood
Blood Volume
Pharmacokinetics
Bronchopulmonary Dysplasia
Phlebotomy
Tandem Mass Spectrometry
Surface-Active Agents
Population
Pediatrics
High performance liquid chromatography
High Pressure Liquid Chromatography
Mass spectrometry
Sampling

Keywords

  • Budesonide
  • Dried blood spots
  • Premature neonates
  • UHPLC-MS/MS

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

Cite this

Development and validation of an assay for quantifying budesonide in dried blood spots collected from extremely low gestational age neonates. / Rower, Joseph E.; Anderson, David J.; Sherwin, Catherine M.; Reilly, Christopher A.; Ballard, Philip L.; McEvoy, Cynthia (Cindy); Wilkins, Diana G.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 167, 15.04.2019, p. 7-14.

Research output: Contribution to journalArticle

Rower, Joseph E. ; Anderson, David J. ; Sherwin, Catherine M. ; Reilly, Christopher A. ; Ballard, Philip L. ; McEvoy, Cynthia (Cindy) ; Wilkins, Diana G. / Development and validation of an assay for quantifying budesonide in dried blood spots collected from extremely low gestational age neonates. In: Journal of Pharmaceutical and Biomedical Analysis. 2019 ; Vol. 167. pp. 7-14.
@article{413d784399ab474cabe87f133a8d637b,
title = "Development and validation of an assay for quantifying budesonide in dried blood spots collected from extremely low gestational age neonates",
abstract = "Budesonide is a potential therapeutic option for the prevention of bronchopulmonary dysplasia in mechanically ventilated premature neonates. The dose and concentrations of budesonide that drive effective prophylaxis are unknown, due in part to the difficulty in obtaining serial blood samples from this fragile population. Of primary concern is the limited total blood volume available for collection for the purposes of a pharmacokinetic study. Dried blood spots (DBS), which require the collection of <200 μL whole blood to fill an entire card, are an attractive low-blood volume alternative to traditional venipuncture sampling. We describe a simple and sensitive method for determining budesonide concentrations in DBS using an ultra-high-performance liquid chromatography – tandem mass spectrometry assay. Budesonide was liberated from a single 6 mm punch using a basified methyl tert-butyl ether extraction procedure. The assay was determined to be accurate and precise in the dynamic range of 1 to 50 ng/mL. The validated assay was then successfully applied to DBS collected as part of a multi-center, dose-escalation study of budesonide administered in surfactant via intra-tracheal instillation to premature neonates between 23 and 28 weeks gestational age. These findings show that DBS are a useful technique for collecting pharmacokinetic samples in premature neonates and other pediatric populations.",
keywords = "Budesonide, Dried blood spots, Premature neonates, UHPLC-MS/MS",
author = "Rower, {Joseph E.} and Anderson, {David J.} and Sherwin, {Catherine M.} and Reilly, {Christopher A.} and Ballard, {Philip L.} and McEvoy, {Cynthia (Cindy)} and Wilkins, {Diana G.}",
year = "2019",
month = "4",
day = "15",
doi = "10.1016/j.jpba.2019.01.048",
language = "English (US)",
volume = "167",
pages = "7--14",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
issn = "0731-7085",
publisher = "Elsevier",

}

TY - JOUR

T1 - Development and validation of an assay for quantifying budesonide in dried blood spots collected from extremely low gestational age neonates

AU - Rower, Joseph E.

AU - Anderson, David J.

AU - Sherwin, Catherine M.

AU - Reilly, Christopher A.

AU - Ballard, Philip L.

AU - McEvoy, Cynthia (Cindy)

AU - Wilkins, Diana G.

PY - 2019/4/15

Y1 - 2019/4/15

N2 - Budesonide is a potential therapeutic option for the prevention of bronchopulmonary dysplasia in mechanically ventilated premature neonates. The dose and concentrations of budesonide that drive effective prophylaxis are unknown, due in part to the difficulty in obtaining serial blood samples from this fragile population. Of primary concern is the limited total blood volume available for collection for the purposes of a pharmacokinetic study. Dried blood spots (DBS), which require the collection of <200 μL whole blood to fill an entire card, are an attractive low-blood volume alternative to traditional venipuncture sampling. We describe a simple and sensitive method for determining budesonide concentrations in DBS using an ultra-high-performance liquid chromatography – tandem mass spectrometry assay. Budesonide was liberated from a single 6 mm punch using a basified methyl tert-butyl ether extraction procedure. The assay was determined to be accurate and precise in the dynamic range of 1 to 50 ng/mL. The validated assay was then successfully applied to DBS collected as part of a multi-center, dose-escalation study of budesonide administered in surfactant via intra-tracheal instillation to premature neonates between 23 and 28 weeks gestational age. These findings show that DBS are a useful technique for collecting pharmacokinetic samples in premature neonates and other pediatric populations.

AB - Budesonide is a potential therapeutic option for the prevention of bronchopulmonary dysplasia in mechanically ventilated premature neonates. The dose and concentrations of budesonide that drive effective prophylaxis are unknown, due in part to the difficulty in obtaining serial blood samples from this fragile population. Of primary concern is the limited total blood volume available for collection for the purposes of a pharmacokinetic study. Dried blood spots (DBS), which require the collection of <200 μL whole blood to fill an entire card, are an attractive low-blood volume alternative to traditional venipuncture sampling. We describe a simple and sensitive method for determining budesonide concentrations in DBS using an ultra-high-performance liquid chromatography – tandem mass spectrometry assay. Budesonide was liberated from a single 6 mm punch using a basified methyl tert-butyl ether extraction procedure. The assay was determined to be accurate and precise in the dynamic range of 1 to 50 ng/mL. The validated assay was then successfully applied to DBS collected as part of a multi-center, dose-escalation study of budesonide administered in surfactant via intra-tracheal instillation to premature neonates between 23 and 28 weeks gestational age. These findings show that DBS are a useful technique for collecting pharmacokinetic samples in premature neonates and other pediatric populations.

KW - Budesonide

KW - Dried blood spots

KW - Premature neonates

KW - UHPLC-MS/MS

UR - http://www.scopus.com/inward/record.url?scp=85061027926&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061027926&partnerID=8YFLogxK

U2 - 10.1016/j.jpba.2019.01.048

DO - 10.1016/j.jpba.2019.01.048

M3 - Article

VL - 167

SP - 7

EP - 14

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

ER -