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Comparison of gas chromatography and receptor bioassay in the determination of diazepam in plasma after conventional tablets and controlled release capsules.

Plasma levels of diazepam and its metabolites were compared after a controlled release formulation and a regular tablet. Both gas chromatographic analysis of plasma diazepam and desmethyldiazepam and radioreceptor assay of total benzodiazepine activity were used. Also the concentrations of benzodiazepine in saliva samples were analyzed by radioreceptor assay. A typical initial plasma peak was seen after the regular tablet but not after the controlled release capsule. Hence the excessive initial sedation can be avoided and the risk of abuse reduced. Desmethyldiazepam increased for about two days after a single dose of diazepam. The receptor assay correlated in general with the sum of diazepam and its desmethyl derivative. The saliva assay gave about 2.5% of the plasma total benzodiazepine which correlates well with the expected free benzodiazepine. It seems that both the plasma radioreceptor assay and the saliva assay can be used to monitor the total benzodiazepine concentration.