Dialysis as an on-line sample-pretreatment technique for column liquid chromatography: influence of experimental variables upon the determination of benzodiazepines in human plasma

N.C. van de Merbel, J M Teule, H Lingeman, U A Brinkman

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An evaluation is provided of dialysis, coupled on-line to column liquid chromatography, as a sample pretreatment procedure for macromolecule-containing biological samples. The influence of parameters such as acceptor phase flow rate, temperature, hydrophobicity of the analytes, pH, ionic strength and viscosity of the sample on the recovery and rate of dialysis is studied. In addition, methods to reduce the degree of drug-protein binding and thereby improve the recovery are reported. Diazepam, nitrazepam and oxazepam are used as model compounds. A method is reported for the fully automated determination of these compounds in human plasma using only 100 microliters of sample. Data on repeatability, linearity and detectability are given.

Original languageEnglish
Pages (from-to)225-33
Number of pages9
JournalJournal of Pharmaceutical and Biomedical Analysis
Issue number2-3
Publication statusPublished - 1-Feb-1992
Externally publishedYes


  • Anti-Anxiety Agents
  • Blood Proteins
  • Chromatography, Liquid
  • Dialysis
  • Diazepam
  • Humans
  • Hydrogen-Ion Concentration
  • Nitrazepam
  • Osmolar Concentration
  • Oxazepam
  • Protein Binding
  • Temperature
  • Viscosity

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