Liquid-chromatographic determination of eight tri- and tetracyclic antidepressants and their major active metabolites.

A "high-performance" liquid-chromatographic method is presented for monitoring the therapeutic concentrations, in plasma, of eight tri- and tetracyclic antidepressants (amitriptyline, nortriptyline, imipramine, desipramine, doxepin, clomipramine, maprotiline, and protriptyline) and their major active metabolites. One of two internal standards is added to 0.5 mL of drug-containing plasma, the pH is adjusted to about 9.5 with borate buffer, and the sample is extracted with isoamyl alcohol in hexane. The extracts are chromatographed on a column of silica and absorbance of the effluent is measured at either 214 or 254 nm. Chromatographic response is linearly related to concentration for all components over a 5-500 ng range. Analytical recovery of the drugs and metabolites from plasma is approximately 75 to 85% at low and high concentrations. Within-run and day-to-day precision (CV) is less than 5% for both high and low concentrations of most of these drugs and metabolites. Parallel analysis of clinical samples by gas chromatography indicates that results by the two techniques are comparable. We report some results of therapeutic monitoring of clinical samples.