Monitoring Serum Concentrations of Clomipramine and Metabolites: Fluorescence Polarization Immunoassay Versus High Performance Liquid Chromatography

This study compared fluorescence polarization immunoassay (FPIA) with a high performance liquid chromatographic (HPLC) method from the point of view of their applicability to therapeutic drug monitoring of patients treated with clomipramine alone. Blood was withdrawn from 20 depressed inpatients (54 ± 14 years) under steady state conditions. The FPIA determined total tricyclic antidepressant (TCA) concentrations with day to day variability below 11 %. The automated HPLC method separated clomipramine, N-desmethylclomipramine, 8-hydroxyclomipramine and 8-hydroxydesmethylclomipramine with interassay coefficients of variance below 12 %. The conceptions measured by FPIA were similar to HPLC results. Total TCA concentrations measured by FPIA and the sum of clomipramine and desmethylclomipramine measured by HPLC correlated significantly (r = 0.780 and p < 0.01). However, 40 % of individual FPIA determinations yielded results that differed by more than 50 % from the HPLC concentrations. Changes in clinical rates were related only to TCA serum concentrations that had been analyzed by HPLC. It is concluded that the semiquantitative FPIA is unsuitable for therapeutic drug monitoring in patients under clomipramine treatment, whereas the differential analysis of clomipramine and metabolites by HPLC is informative and can be used to improve the antidepressant drug treatment.