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 pati ents treated with clomipramine alone. Blood was withdrawn from 20 depr essed inpatients (54+/-14 years) under steady state conditions. The FP IA 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-hy droxydesmethylclomipramine with interassay coefficients of variance be low 12%. The concetrations measured by FPIA were similar to HPLC resul ts. Total TCA concentrations measured by FPIA and the sum of clomipram ine and desmethylclomipramine measured by HPLC correlated significantl y (r=0.780 and p<0.01). However, 40% of individual FPIA determinations yielded results that differed by more than 50% from the HPLC concentr ations. Changes in clinical rates were related only to TCA serum conce ntrations that had been analyzed by HPLC. It is concluded that the sem iquantitative FPIA is unsuitable for therapeutic drug monitoring in pa tients under clomipramine treatment, whereas the differential analysis of clomipramine and metabolites by HPLC is informative and can be use d to improve the antidepressant drug treatment.