[Determination of N-demethyldiazepam and its metabolite oxazepam in plasma by HPLC and their pharmacokinetics in rats]

Yao Xue Xue Bao. 1995;30(9):655-61.
[Article in Chinese]

Abstract

A simple rapid and sensitive HPLC method for simultaneous determination of N-demethyldiazepam and its metabolite oxazepam in both human and rat plasma was described. A reversed phase C18 column equipped with a 240 nm detector were selected. Diazepam was used as internal standard. The mobile phase consisted of acetonitrile--0.01 mol.L-1 sodium acetate buffer (pH 3.8, 33.3: 66.6 v/v). The retention time for N-demethyldiazepam, oxazepam and internal standard were 4.85 min, 2.8 min and 8.5 min, respectively. The lower detection limits for oxazepam and N-demethyldiazepam were 10 ng.ml-1 and 7 ng.ml-1, respectively. The precisions (RSD%, n = 5) of within-day and day-to-day were less than 6% and 10% and their absolute recoveries were 74% and 86%, respectively. The pharmacokinetic characteristics of N-demethyldiazepam in Sprague-Dawley rats after a single oral dose of 2.5 mg.kg-1 was investigated by this method. The concentration-time curve was fitted to a two-compartment open model. Its main pharmacokinetic parameters were: Tmax = 0.24 h, Cmax = 1211.78 ng.ml-1, T1/2 beta = 2.84 h, AUC = 1264 ng.ml-1.h-1.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / blood*
  • Anti-Anxiety Agents / pharmacokinetics
  • Chromatography, High Pressure Liquid / methods
  • Humans
  • Male
  • Nordazepam / blood*
  • Nordazepam / pharmacokinetics*
  • Oxazepam / blood*
  • Oxazepam / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Anti-Anxiety Agents
  • Nordazepam
  • Oxazepam