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.
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Abbreviations
- 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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Woestenborghs, R., Timmerman, P., Van Peer, A., Heykants, J. (1988). The Use of Stable-Isotope Methodology in Pharmacokinetic Studies Involving Flunarizine. In: Reid, E., Robinson, J.D., Wilson, I.D. (eds) Bioanalysis of Drugs and Metabolites, Especially Anti-Inflammatory and Cardiovascular. Methodological Surveys in Biochemistry and Analysis, vol 18 A. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9424-3_18
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DOI: https://doi.org/10.1007/978-1-4757-9424-3_18
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