Determination of Desmethyldiazepam in Plasma by Electron-Capture GLC: Application to Pharmacokinetic Studies of Clorazepate

Abstract

Plasma desmethyldiazepam concentrations were quantitated by a rapid and sensitive technique using electron-capture GLC. Following addition of diazepam as the internal standard, plasma is extracted at physiological pH into benzene–isoamyl alcohol. The extract is evaporated to dryness and reconstituted with toluene–isoamyl alcohol prior to chromatography. Both diazepam and desmethyldiazepam are quantitatively extracted. The variation of identical samples is 596, and the sensitivity is 5ng of desmethyldiazepam/ml of original sample. The method is applicable to Dharmacokinetic studies of clorazepate, a benzodiazepine derivative transformed to desmethyldiazepam prior to absorption.