Methods are described for the determination of amitriptyline, imipramine and orphenadrine in some antidepressant drugs. They are based on a prior reaction with ammonium reineckate to form 11 water-insoluble drugreineckate ion-pair complexes. These complexes are (i) used as ion-exchangers in liquid-membrane electrodes responsive to the drug cations, (ii) extracted with nitrobenzene or dissolved in acetonitrile and spectrophotometrically measured at 525 nm and (iii) dissolved in 90% acetone followed by nebulization in an air-acetylene flame for atomic absorption spectrometric measurements of Cr at 358.6 nm. The reaction and monitoring conditions are optimized to permit determination of as little as 10 g/ml of the drugs. Determination of the drugs in some pharmaceutical preparations shows an average recovery of 98.8% of the nominal and a mean standard deviation of 0.8%. The results compare favorably with data obtained by the United States and British Pharmacopoeia methods.