Nanogram-range determination of plasma imipramine by gas-liquid chromatography using a selective nitrogen/phosphorus detector.

A sensitive and specific gas chromatographic method for the quantitative determination of plasma concentrations resulting from a single normal therapeutic dose of imipramine has been developed and is descriged. After extraction into a mixture of n-heptane/isoamyl alcohol (98.5:1.5), imipramine is well separated from its main metabolite, desmethylimipramine, and both compounds are detected using a selective detector operating in the N/P mode. The procedure permits the rapid routine quantitative analysis of relatively small plasma volumes (1-2 ml) containing as little as 1-2 ng of imipramine. No interference from the biological matrix is apparent. The suitability of the method for the analysis of biological samples was tested by studying the time of course of imipramine plasma concentrations in normal human volunteers, after administration of a single therapeutic dose.