Determination of submicrogram quantities of clonidine in biological fluids.

A sensitive and specific GLC method using electron-capture detection was developed for clonidine in plasma and urine. Di-perfluoroacyl derivatives of both clonidine and the 4-methyl analog of clonidine (used as an internal standard) were formed, and an extraction process was developed for the removal of excess derivatization reagent and endogenous biological compounds; the assay permitted quantification of 25 pg of clonidine/ml in a 4-ml plasma sample. The assay was used to elucidate the time course of plasma concentrations in a normotensive subject following oral administration of 50, 100, and 200 microgram of clonidine hydrochloride and also to determine unchanged drug excreted in the urine.