Quantitative Gas‐Liquid Chromatographic Determination of Clonidine in Plasma

Abstract

A highly sensitive gas-liquid chromatographic method with electron capture detection of clonidine [an anti-hypertensive, sedative and analgesic] in plasma is described. The alkaline samples (100-200 .mu.l) are extracted into cyclohexane-butanol (9:1), re-extracted into 0.1 N H2SO4, made alkaline and back-extracted into cyclohexane-butanol. The pentafluorobenzyl derivatives of clonidine and the internal standard 2,-(2,4-dichlorophenylamino)-2-imidazoline are then formed and excess of reagent is removed by solvent extractions. The minimum detectable quantity of clonidine and the internal standard are 2.5 .cntdot. 10-16 mol/s (3.3 pg) and 2.8 .cntdot. 10-16 mol/s (5.9 pg), respectively. The smallest amount of clonidine which can be determined in plasma samples with a precision of less than 20% SD is 200 pg. The time course of clonidine in plasma after i.v. administration of 500 .mu.g/kg to rats revealed that the data best fit a 3-compartment open model.