Rapid radioisotopic procedure for determination of nortriptyline in plasma

With the widespread use of tricyclic antidepressant drugs, the relationship between the concentration of the drug in the plasma and the therapeutic response is of considerable interest. We describe a double-isotope derivative dilution procedure for measuring plasma nortriptyline. In the method, [14C]nortriptyline is used for estimating procedural losses and [3H]acetic anhydride for derivative formation. The assay is rapid and adequately specific, sensitive, precies, and reproducible for routine clinical use. We used it to investigate the variation in steady-state drug concentrations in plasma of persons who were on a 150 mg/day dose of nortriptyline. Intra-individual variation from day to day was 10-14%. This variation was not significantly affected by the dosage schedule, the time of sampling after an oral dose, or the storage of the plasma samples. For 19 patients on 150 mg of nortriptyline per day, the mean concentration in plasma was 181 +/- 22 (SE) mug/liter, a value that compares well with our previous findings and those of other groups.