Stabilization and HPLC Analysis of Betamethasone Sodium Phosphate in Plasma

Mahesh N. Samtani, Matthias Schwab, Peter W. Nathanielsz, William J. Jusko

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The analysis of corticosteroid prodrugs in pharmacokinetic (PK) studies poses the risk of overestimation of corticosteroid concentrations due to in vitro hydrolysis of prodrugs after sample collection. This study tests the effectiveness of enzyme inhibitors as stabilizers for betamethasone sodium phosphate (BSP) in pregnant sheep plasma samples collected during PK studies with betamethasone (BET) and provides simultaneous high-performance liquid chromatography analysis of BSP and BET. A rapid, sensitive, and specific ion-paired reversed-phase high-performance liquid chromatography assay for simultaneous measurement of BET and BSP in plasma was developed. This assay was used for analyzing samples from an in vitro prodrug hydrolysis study. Enzyme inhibitors tested were sodium arsenate (Na2HAsO4) and ethylenediaminetetraacetic acid. The BSP was administered intramuscularly to three pregnant sheep to assess in vivo PK. Samples were split with part treated with Na2HAsO4 and part left natural. In vitro hydrolysis of BSP in plasma to BET could be completely inhibited by Na2HAsO 4, but not by ethylenediaminetetraacetic acid. The PK study showed lower concentrations of BET in samples with Na2HAsO4 compared with natural samples. This study demonstrates that artifacts in PK profiles of corticosteroids due to in vitro prodrug hydrolysis can be prevented by sample treatment with enzyme inhibitors.

Original languageEnglish (US)
Pages (from-to)726-732
Number of pages7
JournalJournal of Pharmaceutical Sciences
Volume93
Issue number3
DOIs
StatePublished - Mar 2004
Externally publishedYes

Keywords

  • Betamethasone sodium phosphate
  • Corticosteroids
  • Enzyme inhibitors
  • HPLC
  • Pharmacokinetics
  • Pregnancy
  • Prodrugs
  • Sheep
  • Sodium arsenate
  • Stability

ASJC Scopus subject areas

  • Pharmaceutical Science

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