DIRECT DETECTION OF THERAPEUTIC CONCENTRATIONS OF TRICYCLIC ANTIDEPRESSANTS IN WHOLE HEMOLYZED BLOOD USING THE EMITTOX SERUM TRICYCLIC ANTIDEPRESSANT ASSAY

A simple, rapid, and sensitive method for the direct detection of tricyclic antidepressant drugs in whole hemolyzed blood using an enzyme immunoassay technique is described. A methanolic extract prepared from as little as 200-mu-L of whole blood is analyzed directly using the EMIT(tox) serum tricyclic antidepressant assay, allowing it to be used with whole blood rather than only serum. The minimum detectable concentration of most of the tricyclics is in the range of 25-50 ng/mL, a therapeutic or subtherapeutic, rather than toxic, concentration. The proposed assay shows excellent precision with a mean coefficient of variation (CV) of 0.7%. The cross-reactivity of 12 tricyclic antidepressant drugs is reported. The relationship between drug structure and relative assay response is thoroughly investigated. The relative assay response due to each of nine separate molecular features is calculated. The relationship between the molecular structure and EMIT assay response on a molar basis is shown to be not only quantitative but also additive. This should allow the quantitative prediction of EMIT assay response for drugs or compounds having similar structures.