Methods for the determination of lorazepam and chlordiazepoxide and metabolites in brain tissue. A comparison with plasma concentrations in the rat.

Rapid and sensitive methods are described for determining lorazepam and for determining chlordiazepoxide and its metabolites in brain tissue of the rat. Lorazepam was determined by means of solvent extraction and electron-capture gas-liquid chromatography and concentrations as low as 5 ng/g tissue could be measured. High-performance liquid chromatography with UV detection was used to determine chlordiazepoxide and its metabolites and was sensitive to 0.1 micrograms/g tissue. The methods were used to investigate the brain and plasma pharmacokinetics of these compounds in animals that had been chronically treated with lorazepam or chlordiazepoxide. In both experiments brain and plasma levels of all compounds assayed were found to correlate highly.