Gas chromatography nitrogen phosphorous detection (GC-NPD) assay of tofisopam in human plasma for pharmacokinetic evaluation

Maria Tóth, Andrea Bereczki, Sándor Drabant, Katalin Balogh Nemes, Bálint Varga, Gyula Grézal, Judit Tömlo, Géza Lakner, Imre Klebovich

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10 Citations (Scopus)

Abstract

Tofisopam (1-(3,4-dimethoxyphenyl)-4-methyl-5-ethyl-7,8-dimethoxy-5H-2,3-benzodiaz epine) has been shown to be an effective anxiolytic agent in the wide-ranging clinical practice. A high sensitive gas chromatography nitrogen phosphorous detection (GC-NPD) bioanalytical method was developed and validated for the purpose of pharmacokinetic study of tofisopam. A liquid-liquid extraction method was used for the sample preparation. The mean recovery for tofisopam was 69.8% and the inter- and intra-day precision values were well below the 15% limit established for bioanalytical methods. A similar compound, girizopam was used as internal standard. The assay was linear in the 5-500 ng/ml range corresponding to therapeutically relevant plasma levels. The concentrations of the compound were measured in the plasma samples of 12 healthy male volunteers and the pharmacokinetic parameters were determined from the plasma concentration-time data. A rapid absorption and distribution, relatively short biological half-life and considerable inter-individual variation in the plasma concentration levels of parent compound were the main characteristics of the pharmacokinetics of tofisopam. According to these results, the new (GC-NPD) bioanalytical method proved to be capable of measuring concentration of tofisopam in human plasma and was successfully applied in a single dose pharmacokinetic study.

Original languageEnglish
Pages (from-to)1354-1359
Number of pages6
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume41
Issue number4
DOIs
Publication statusPublished - Jun 16 2006

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Keywords

  • Gas chromatography nitrogen phosphorous detection (GC-NPD)
  • Pharmacokinetics
  • Single dose clinical study
  • Tofisopam

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

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