Stable isotope coadministration methodology for the estimation of the fraction of imipramine metabolized to desipramine.

The application of a stable isotope coadministration technique for estimating the fraction (fm) of imipramine (IP) that is converted to desipramine (DMI) is described. Four healthy male subjects received 25 mg of IP-d4 hydrochloride orally with 25 mg of DMI hydrochloride. The plasma concentrations of IP-d4, DMI-d4, and DMI were determined by capillary gas chromatography-mass spectrometry-selected ion monitoring using d8 analogues as internal standards. The fm values, calculated from the ratio of the area under the plasma concentration-time curve of DMI-d4 to that of DMI, varied from 0.54 to 0.85.