Valproic acid binding to human serum albumin and human plasma: Effects of ph variation and buffer composition in equilibrium dialysis

Fiorenzo Albani, Roberto Riva, Manuela Contin, Agostino Baruzzi

Research output: Contribution to journalArticle

Abstract

The binding of valproic acid (VPA) to human serum albumin (HSA) and to pooled human plasma has been investigated by using equilibrium dialysis with three different dialysis solutions: phosphate buffer (solution I), Krebs solution (solution II), and Krebs solution without calcium (solution III). The effect of pH variation from 6.4 to 8.2 has been also investigated. VPA free fraction increased by increasing pH with all the dialysis solutions (from 4.1% at pH 6.4 to 9.4% at pH 8.2 with solution I, from 8.1% to 11.3% with solution II, and from 10.6% to 14.3% with solution III, in plasma). At each pH value, free fraction obtained with solution III was the highest and that obtained with solution I was the lowest. Data in plasma and HSA solution were similar. In a separate experiment we compared (at pH 7.4, with plasma) the three more frequently used dialysis solutions: phosphate buffer, phosphate buffer with NaCl, and Krebs solution. They gave, respectively, a mean VPA free fraction of 7.8, 10.3, and 12.7%. These findings can explain the wide range of VPA free fraction values reported in the literature. Researchers intending to determine VPA free concentration by equilibrium dialysis should take into account these methodological aspects.

Original languageEnglish
Pages (from-to)31-33
Number of pages3
JournalTherapeutic Drug Monitoring
Volume6
Issue number1
Publication statusPublished - 1984

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Plasma (human)
Dialysis
Valproic Acid
Serum Albumin
Buffers
Chemical analysis
Dialysis Solutions
Phosphates
Plasmas
Research Personnel
Calcium
Krebs-Ringer solution

Keywords

  • Buffer effect on binding
  • Equilibrium dialysis
  • PH effect on binding
  • Valproic acid binding

ASJC Scopus subject areas

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

Cite this

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title = "Valproic acid binding to human serum albumin and human plasma: Effects of ph variation and buffer composition in equilibrium dialysis",
abstract = "The binding of valproic acid (VPA) to human serum albumin (HSA) and to pooled human plasma has been investigated by using equilibrium dialysis with three different dialysis solutions: phosphate buffer (solution I), Krebs solution (solution II), and Krebs solution without calcium (solution III). The effect of pH variation from 6.4 to 8.2 has been also investigated. VPA free fraction increased by increasing pH with all the dialysis solutions (from 4.1{\%} at pH 6.4 to 9.4{\%} at pH 8.2 with solution I, from 8.1{\%} to 11.3{\%} with solution II, and from 10.6{\%} to 14.3{\%} with solution III, in plasma). At each pH value, free fraction obtained with solution III was the highest and that obtained with solution I was the lowest. Data in plasma and HSA solution were similar. In a separate experiment we compared (at pH 7.4, with plasma) the three more frequently used dialysis solutions: phosphate buffer, phosphate buffer with NaCl, and Krebs solution. They gave, respectively, a mean VPA free fraction of 7.8, 10.3, and 12.7{\%}. These findings can explain the wide range of VPA free fraction values reported in the literature. Researchers intending to determine VPA free concentration by equilibrium dialysis should take into account these methodological aspects.",
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author = "Fiorenzo Albani and Roberto Riva and Manuela Contin and Agostino Baruzzi",
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T2 - Effects of ph variation and buffer composition in equilibrium dialysis

AU - Albani, Fiorenzo

AU - Riva, Roberto

AU - Contin, Manuela

AU - Baruzzi, Agostino

PY - 1984

Y1 - 1984

N2 - The binding of valproic acid (VPA) to human serum albumin (HSA) and to pooled human plasma has been investigated by using equilibrium dialysis with three different dialysis solutions: phosphate buffer (solution I), Krebs solution (solution II), and Krebs solution without calcium (solution III). The effect of pH variation from 6.4 to 8.2 has been also investigated. VPA free fraction increased by increasing pH with all the dialysis solutions (from 4.1% at pH 6.4 to 9.4% at pH 8.2 with solution I, from 8.1% to 11.3% with solution II, and from 10.6% to 14.3% with solution III, in plasma). At each pH value, free fraction obtained with solution III was the highest and that obtained with solution I was the lowest. Data in plasma and HSA solution were similar. In a separate experiment we compared (at pH 7.4, with plasma) the three more frequently used dialysis solutions: phosphate buffer, phosphate buffer with NaCl, and Krebs solution. They gave, respectively, a mean VPA free fraction of 7.8, 10.3, and 12.7%. These findings can explain the wide range of VPA free fraction values reported in the literature. Researchers intending to determine VPA free concentration by equilibrium dialysis should take into account these methodological aspects.

AB - The binding of valproic acid (VPA) to human serum albumin (HSA) and to pooled human plasma has been investigated by using equilibrium dialysis with three different dialysis solutions: phosphate buffer (solution I), Krebs solution (solution II), and Krebs solution without calcium (solution III). The effect of pH variation from 6.4 to 8.2 has been also investigated. VPA free fraction increased by increasing pH with all the dialysis solutions (from 4.1% at pH 6.4 to 9.4% at pH 8.2 with solution I, from 8.1% to 11.3% with solution II, and from 10.6% to 14.3% with solution III, in plasma). At each pH value, free fraction obtained with solution III was the highest and that obtained with solution I was the lowest. Data in plasma and HSA solution were similar. In a separate experiment we compared (at pH 7.4, with plasma) the three more frequently used dialysis solutions: phosphate buffer, phosphate buffer with NaCl, and Krebs solution. They gave, respectively, a mean VPA free fraction of 7.8, 10.3, and 12.7%. These findings can explain the wide range of VPA free fraction values reported in the literature. Researchers intending to determine VPA free concentration by equilibrium dialysis should take into account these methodological aspects.

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