title: Gas chromatography nitrogen phosphorous detection (GC-NPD) assay of tofisopam in human plasma for pharmacokinetic evaluation.
abstract: Tofisopam (1-(3,4-dimethoxyphenyl)-4-methyl-5-ethyl-7,8-dimethoxy-5H-2,3-benzodiazepine) 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.
authors: EGIS Pharmaceuticals Ltd., Research and Development Directorate, Keresztúri út 30-38, H-1106 Budapest, Hungary. clinpharm.rd@egis.hu
authors: Maria
authors: M
authors: Tóth
authors: Andrea
authors: A
authors: Bereczki
authors: Sándor
authors: S
authors: Drabant
authors: Katalin Balogh
authors: KB
authors: Nemes
authors: Bálint
authors: B
authors: Varga
authors: Gyula
authors: G
authors: Grézal
authors: Judit
authors: J
authors: Tömlo
authors: Géza
authors: G
authors: Lakner
authors: Imre
authors: I
authors: Klebovich