Determination of unbound valproic acid concentration in plasma by equilibrium dialysis and gas-liquid chromatography: Methodological aspects and observations in epileptic patients

Roberto Riva, Fiorenzo Albani, Agostino Baruzzi, Ianna Galvani, Emilio Perucca

Research output: Contribution to journalArticlepeer-review

Abstract

An equilibrium dialysis technique for the separation of the free (unbound) concentration of valproic acid (VPA) in plasma is described together with a sensitive gas chromatographic assay for the quantitative determination of the drug in the dialysate. The overall coefficient of variation of the method was below 10%. By using a high permeability membrane, equilibration of the drug between the plasma and the buffer compartments was obtained after about 45 min at 37°C. With this dialysis time, dilutional changes in the plasma compartment were negligible and there was no significant change in the plasma-free fatty acid (FFA) concentration. No passage of protein into the buffer solution was detected. When dialysis was prolonged for up to 4 h, a significant elevation in plasma FFA (with a corresponding rise in free VPA fraction) was observed. Storage of plasma samples at temperatures ranging from 4 to 37°C for 8 h or longer before dialysis also resulted in an increased value of free VPA fraction and FFA concentration. The two effects were significantly correlated. The free fraction of VPA was found to increase with increasing total plasma concentration. This effect was observed both in vitro and in vivo in the plasma of 91 patients receiving chronic VPA therapy. The methodological problems of using equilibrium dialysis techniques for determining the free fraction of VPA are highlighted.

Original languageEnglish
Pages (from-to)341-352
Number of pages12
JournalTherapeutic Drug Monitoring
Volume4
Issue number4
Publication statusPublished - 1982

Keywords

  • Equilibrium dialysis
  • Valproic acid-Plasma protein binding

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Public Health, Environmental and Occupational Health

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