A COMPARISON OF HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND FLUORESCENCE POLARIZATION IMMUNOASSAY FOR THERAPEUTIC DRUG-MONITORING OF TRICYCLIC ANTIDEPRESSANTS

Although the manufacturer of the polyclonal fluorescence polarization immunoassay (FPIA) for tricyclic antidepressants (TCA) only recommends its use in the diagnosis of overdose, the assay is nevertheless widel y used in therapeutic drug monitoring. Using plasma samples from 337 p atients taking one of eight different tricyclic antidepressants, the a uthors investigated the performance of the TDx assay procedure for eig ht different TCAs by comparison to specific high-performance liquid ch romatography (HPLC) assay methods. The regression correlation between the TDx assay value and that for active tricyclic measured by HPLC was poor (r(2) < 0.9) for amitriptyline, clomipramine, dothiepin, and dox epin. The regression line for amitriptyline also had a significant pos itive y-axis intercept. Moreover, the TDx method overestimated the con centration of active drug to an extent that varied considerably betwee n different TCAs and within the usual therapeutic range for a single T CA, The authors conclude that the TDx assay is probably satisfactory f or routine TDM of desipramine, imipramine, nortriptyline, and trimipra mine. However, it significantly overestimates therapeutic concentratio ns of amitriptyline, clomipramine, dothiepin, and doxepin. The use of TDx and HPLC assay methods by different laboratories for sequential th erapeutic drug monitoring of TCAs in the same patient may confuse phys icians and confound dose adjustment and patient management. Although t heir study shows that the TDx assay can give satisfactory therapeutic drug monitoring results for some drugs, the authors conclude that its use should be restricted to the evaluation of overdose as recommended by the manufacturer.