The Use of Stable-Isotope Methodology in Pharmacokinetic Studies Involving Flunarizine

  • Robert Woestenborghs
  • Philip Timmerman
  • Achiel Van Peer
  • Jos Heykants
Chapter
Part of the Methodological Surveys in Biochemistry and Analysis book series (MSBA, volume 18 A)

Abstract

Co-administration of a drug and a suitable isotopomer can substantially reduce the number of study phases and subjects required in bioavailability studies. Flunarizine is particularly suited to stableisotope methodology, because of its excellent GC properties and its long half-life in plasma. We therefore developed a sensitive GC-MS procedure for the simultaneous determination of flunarizine and its d 4 * isotopomer. After analyte extraction from plasma, capillary GC-MS is performed in either the EI or the PCI mode using isobutane as reagent gas, resulting in sensitivity limits of 0.2 and 0.1 ng/ml respectively. With the EI mode, plasma levels were determined in 3 volunteers given a d0/d4 mixture (10 + 10 mg). The pharmacokinetics showed no isotope effect; thus the approach was well suited to bioequivalence studies.

Keywords

Bioequivalence Study Bioavailability Study Analyte Extraction Peripheral Vascular Disorder Janssen Research Foundation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviation

d

deuterium (4 atoms if d 4)

MS

mass spectrometry

EI

electron impact

(P)CI

(positive) chemical ionization

SIM

selected ion monitoring

i.s.

internal standard

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Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Robert Woestenborghs
    • 1
  • Philip Timmerman
    • 1
  • Achiel Van Peer
    • 1
  • Jos Heykants
    • 1
  1. 1.Department of Drug Metabolism and PharmacokineticsJanssen Research FoundationBeerseBelgium

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