A sensitive method for the simultaneous determination in biological fluids of imipramine and desipramine or clomipramine and N-desmethylclomipramine by gas chromatography mass spectrometry.

A procedure is described which permits the simultaneous determination of imipramine and desipramine or clomipramine and N-desmethylclomipramine in serum or plasma for concentrations in the range of 1-200 ng ml-1. Detection limits of 0.2 ng ml-1 for imipramine and 0.1 ng ml-1 for desipramine were demonstrated with a signal-to-noise ratio maintained at 2:1 or better. The method relies on the derivatization of the secondary amines with heptafluorobutyric anhydride and is based on the combined use of gas chromatography, electron impact mass spectrometry and computerized data handling. The assaying procedure is specific, accurate and precise. It is suitable for routine analyses and has sufficient sensitivity to permit monitoring the drug and metabolite levels in human plasma or serum resulting from a single therapeutic dose.