[Determination of N-demethyldiazepam and its metabolite oxazepam in plasma by HPLC and their pharmacokinetics in rats].
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.
Liu
J F
JF
Department of Pharmacology, Beijing Medical University.
Zhang
Y
Y
D000818:Animals; D014151:Anti-Anxiety Agents / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D008297:Male; D003708:Nordazepam / Q000097:blood* / Q000493:pharmacokinetics*; D010076:Oxazepam / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D014151:Anti-Anxiety Agents; D003708:Nordazepam; D010076:Oxazepam