Simultaneous analysis of imipramine and its metabolite desipramine in biological fluids

A method for the simultaneous quantitation of imipramine and its N-demethylated metabolite desipramine at the nanogram level in a single gas chromatograph peak is presented, utilizing gas chromatography-mass spectrometry with selected ion recording. The assay is specific and quantitation is achieved using [2H4]imipramine as the internal standard. The method involves the in situ methylation of desipramine with [2H2]formaldehyde and sodium borohydride to give [2H2]imipramine. Quantitation is then achieved by selected ion recording at m/z 280, 282 and 284, whence the ratio of the ion currents at 280/284 and at 282/284 gives the quantities of imipramine and desipramine respectively.