Gas-liquid chromatographic determination of clonidine and some analogues in rat brain tissue. Brain concentrations and hypotensive activity.

A simple and sensitive gas-liquid chromatographic method has been developed for the quantitative determination of clonidine and some structurally related imidazolidines in rat brain tissue. The aqueous brain homogenates are first purified and then extracted into benzene. Samples are injected directly into the gas chromatograph. The extraction procedure is selective, and the use of a phosphorus-nitrogen detector enables accurate determinations corresponding to brain concentrations down to at least 10ng/g. The rat brain concentrations of clonidine and its derivatives achieved at the moment of maximal decrease in arterial pressure are proportional to the doses administered intravenously, and are not influenced by the effect of the compounds on the blood pressure or by the method of anaesthesia employed. It is concluded that, for the linear part of the dose-response curves for these compounds, the brain concentration is a measure of the hypotensive effect.