Reversed-phase liquid chromatography and gas chromatography/mass fragmentography compared for determination of tricyclic antidepressant drugs.

We compare measurement of the tricyclic antidepressants desipramine, imipramine, nortryptaline, and amitryptaline by reversed-phase "high-performance" liquid chromatography and by gas chromatography/mass fragmentography. The liquid-chromatographic procedure does not require ion-pairing reagents, and involves detection at 215 nm. The within-day and between-day CVs for this method were less than 5% and less than 7%, respectively, and linear-regression analysis of peak height vs concentration for each of the drugs showed excellent correlation (r greater than 0.97) over the range 0-250 microgram/L. Potential interferences with the internal standard (N-desmethyldoxepin) and nortryptaline were oxazepam and N-desmethyldiazepam, respectively, as shown by mass spectrometry. The interference could be circumvented by increasing the column temperature to 50 degrees C. We conclude that reversed-phase liquid chromatography with detection in the far-ultraviolet wavelengths provides an alternative to gas-chromatographic procedures for the tricyclic antidepressants, provided the analyst has prior knowledge of the patient's other medications.