QUANTITATIVE-DETERMINATION OF TRICYCLIC ANTIDEPRESSANTS AND THEIR METABOLITES IN PLASMA BY SOLID-PHASE EXTRACTION (BOND-ELUT TCA) AND SEPARATION BY CAPILLARY GAS-CHROMATOGRAPHY WITH NITROGEN-PHOSPHORUS DETECTION

An analytical method for the simultaneous determination of amitriptyli ne, nortriptyline, imipramine, desipramine, clomipramine, and desmethy lclomipramine in human plasma using promazine as internal standard is described. The method is based on a solid-phase extraction procedure u sing the Bond-Elut TCA columns followed by separation and detection us ing capillary gas chromatography with a specific nitrogen phosphorous detector (GC/NPD). Using the new extraction procedure, the problem of adsorption losses was overcome, and good recoveries were achieved for all compounds tested (>87%). Furthermore, clean extracts free of chrom atographic interferences were obtained. Complete separation of underiv atized, tricyclic antidepressant compounds was achieved in <11 minutes with reliable chromatographic performance. The Limits of detection ra nged from 1.2 to 5.8 mu g/l. Calibration curves, showing goad linearit y, were prepared covering the therapeutic concentrations range expecte d (20 to 500 mu g/l). The interassay precision values (RSD) ranged fro m 4.5% to 9.8%. It is concluded that extraction of amitriptyline, nort riptyline, imipramine, desipramine, clomipramine, and desmethylclomipr amine, with Bond Elut TCA solid-phase columns followed by their detect ion using GC/NPD provides a sensitive and reproducible method that can be easily automated for immediate and routine analysis of clinical sa mples.